DI Groups Research Articles

Oral Magnesium Treatment Reduces Anemia and Levels of Inflammatory Markers in Experimental Diabetes

ABSTRACT Magnesium has been reported to improve glucose utilization in diabetes mellitus. However, information on its effects on anemic and inflammatory markers in diabetes mellitus is limited. This study investigated the effect of oral magnesium (Mg) treatment on some markers of anemia and inflammation in 25 male Wistar rats. Rats (200 ± 15 g) were randomly divided into five groups (n = 5). Group 1 was control (received orally 0.2 mL distilled water daily), group 2 (Diabetic Untreated), group 3 (Diabetic Mg treated—100 mg/kg bw), group 4 (Diabetic Mg treated—250 mg/kg bw), group 5 (Diabetic Insulin treated—1 IU/kg bw). Diabetes was induced with a single dose of alloxan (100 mg/kg intraperitoneal (i.p.)). All treatments were done for 14 days. Anemic and inflammatory markers were investigated on blood samples obtained from each animal using standard laboratory methods. Significant increase (p < 0.05) in total white blood cell (WBC) count was observed in diabetic untreated rats (7.67 ± 0.397 × 109/L) compared to control (5.88 ± 0.25 × 109/L), DMg 100 (5.86 ± 0.74 × 109/L) and DMg 250 (5.06 ± 0.78 × 109/L). Hemoglobin concentration, packed cell volume (PCV) and red blood cell (RBC) count was decreased (p < 0.05) in DU compared to control, DMg 100, and DI rats. Erythrocyte sedimentation rate (ESR) was significantly increased (p < 0.05) in DU compared to control, DMg 100, DMg 250, and DI groups. Fibrinogen level was increased (p < 0.05) in DU rats (0.44 ± 0.02 g/dL) compared to control(0.26 ± 0.02 g/dL). Values obtained in DMg 100 (0.30 ± 0.03 g/dL), DMg 250 (0.22 ± 0.04 g/dL), and DI (0.36 ± 0.02 g/dL) rats were comparable to control (0.26 ± 0.02 g/dL). Total protein, albumin, and globulin levels were decreased in DU rats compared to normal control, DMg 100, DMg 250, and DI rats. In conclusion, anemia and increased hematologic and metabolic inflammatory markers may be associated with untreated diabetes mellitus. Treatment of alloxan-induced diabetic rats with magnesium improved the anemic state and reduced hematologic and metabolic inflammatory markers.

Diet and diet combined with chronic aerobic exercise decreases body fat mass and alters plasma and adipose tissue inflammatory markers in obese women

The purpose of this study was to investigate the effect of 6 months aerobic exercise and diet alone or in combination on markers of inflammation (MOI) in circulation and in adipose abdominal tissue (AT) in obese women. Thirty obese subjects were randomized into a 24-week intervention: (1) exercise (EX), (2) diet (DI), and (3) exercise and diet (EXD). Blood samples were collected at baseline, after 12 and 24 weeks. AT biopsies were obtained only at baseline and after 24 weeks. In the EXD and DI groups, the fat loss was after 12 weeks was −13.74 and −7.8 % (P < 0.01) and after 24 weeks was −21.82 and −17 % (P < 0.01) with no changes in the EX group. After 12 and 24 weeks, maximal oxygen consumption (VO2max) was increased by 21.81–39.54 % (P < 0.05) in the EXD group and 18.09–40.95 % in the EX group with no changes in the DI group. In the EXD and DI groups, circulating levels of tumor necrosis factor α and interleukin 6 were decreased after 24 weeks for both groups (P < 0.01). No changes in the EX group. Homeostatic model assessment for insulin resistance decreased (P < 0.05) only after 24 weeks in the EXD group. In AT biopsies, subjects in the EXD and DI groups exhibited a significant decrease in MO (P < 0.01 for all). No changes in AT biopsies were found in the EX group. In conclusion, chronic aerobic exercise was found to have no effects on circulating and AT MOI despite an increased VO2max. Rather important body composition modifications were found to have beneficial effects on circulating and AT MOI in these obese women.

Paternal dapoxetine administration induced deterioration in reproductive performance, fetal outcome, sexual behavior and biochemistry of male rats.

Dapoxetine, a selective serotonin reuptake inhibitor, is considered an antidepressant drug and has been developed for the treatment of premature ejaculation. Hence the objective was to assess whether dapoxetine administration to male rats adversely affect sexual behavior and pregnancy outcomes after mating with untreated female rats. Proven fertile male rats were gavaged with 0, 2.0, 4.0 and 8.0 mg dapoxetine per kg body weight (bw) per day (DC, DI, DII and DIII groups, respectively) for 70 days prior to mating with untreated female rats. Weight gain, organ weights and feed consumption were decreased significantly in the DII and DIII groups. A significant decline in the number of spermatozoa in the DII and DIII groups is attributed to a significant decrease in testosterone, luteinizing hormone and follicle-stimulating hormone. Levels of prolactin were significantly increased in the DII and DIII groups. Rats treated with a high dose of dapoxetine (8.0 mg kg(-1)) showed a significant inhibition in sperm motility and increment in sperm abnormalities. There was a pronounced decrease in fertility index in females mated with males treated chronically with 4.0 and 8.0 mg per kg bw dapoxetine. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by males in the DII and DIII groups reflecting their infertility. The number of implantation sites and the number of viable fetuses were also notably decreased in female rats impregnated by males given 4.0 or 8.0 mg kg(-1) dapoxetine. These findings suggest that the long-term dapoxetine at high dosages causes failure of the fertilization or successful impregnation of the females mated with dapoxetine-treated male rats, which were clearly able to copulate. A detrimental effect of dapoxetine on fertility parameters was also revealed.

Effect and mechanism of propofol on myocardial ischemia reperfusion injury in type 2 diabetic rats

BackgroundPropofol has been reported to have an inhibitory effect on ischemia/reperfusion (I/R) injury in various experimental models by reducing oxidative stress, protecting mitochondrial function and suppressing apoptosis. The aim of this study was to investigate the effect and mechanism of propofol on myocardial I/R injury in type 2 diabetic rats. MethodsA total of 24 streptozotocin (STZ)-induced diabetic rats were randomly divided into three equal groups as follows: the DI group with myocardial I/R, which was induced by occluding the left anterior descending coronary artery for 30min, followed by 2h of reperfusion; the DP group, which underwent I/R and propofol infusion at 6mg·kg−1·h−1; and the DC group, which underwent sham operations without tightening of the coronary sutures. As a control, 24 healthy, age-matched, male Wistar rats were randomly divided into three equal groups: the CI, CP and CC groups. The injured cardiac tissues were removed for microscopic examination after reperfusion. The serum concentrations of nitric oxide (NO) and endothelin (ET-1); the expression of Bax, Bcl-2 and Caspase-3 within the cardiac structures; and the number of apoptotic myocardial cells were measured. ResultsCompared with the baseline levels before ischemia, the serum concentration of ET-1 after 2h of reperfusion was increased in the CI and DI groups, while the concentration of NO in these groups decreased after reperfusion. Compared with the I/R groups, propofol increased the content of NO and decreased the content of ET-1. Compared with the sham operation groups, I/R decreased the ratio of the anti-apoptotic protein Bcl-2 to the pro-apoptotic protein Bax, which resulted in an elevation of the index of apoptosis (AI). In contrast, compared with the I/R group, propofol increased the Bcl-2-to-Bax ratio and decreased the AI. I/R increased the expression of caspase-3 compared with the sham treatment groups, while treatment with propofol reduced caspase-3 expression relative to the I/R groups. ConclusionsThese data suggest that propofol can protect against myocardial ischemia–reperfusion injury in both normal and type 2 diabetic rats, possibly by attenuating endothelial cell injury and inhibiting the apoptosis of cardiomyocytes.

Diet and Diet Combined with Chronic Aerobic Exercise Decreases Body Fat Mass and Alters Plasma and Adipose Tissue Inflammatory Markers in Obese Women

The purpose of this study was to investigate the effect of 6 months aerobic exercise and diet alone or in combination on markers of inflammation (MOI) in circulation and in adipose abdominal tissue (AT) in obese women. Thirty obese subjects were randomized into a 24-week intervention: (1) exercise (EX), (2) diet (DI), and (3) exercise and diet (EXD). Blood samples were collected at baseline, after 12 and 24 weeks. AT biopsies were obtained only at baseline and after 24 weeks. In the EXD and DI groups, the fat loss was after 12 weeks was -13.74 and -7.8 % (P < 0.01) and after 24 weeks was -21.82 and -17 % (P < 0.01) with no changes in the EX group. After 12 and 24 weeks, maximal oxygen consumption (VO2max) was increased by 21.81-39.54 % (P < 0.05) in the EXD group and 18.09-40.95 % in the EX group with no changes in the DI group. In the EXD and DI groups, circulating levels of tumor necrosis factor α and interleukin 6 were decreased after 24 weeks for both groups (P < 0.01). No changes in the EX group. Homeostatic model assessment for insulin resistance decreased (P < 0.05) only after 24 weeks in the EXD group. In AT biopsies, subjects in the EXD and DI groups exhibited a significant decrease in MO (P < 0.01 for all). No changes in AT biopsies were found in the EX group. In conclusion, chronic aerobic exercise was found to have no effects on circulating and AT MOI despite an increased VO2max. Rather important body composition modifications were found to have beneficial effects on circulating and AT MOI in these obese women.

Adiponectin and interleukin-6 levels in insulin-treated diabetic rats with experimental periodontitis

The aim of the study was to compare the serum levels of adiponectin and interleukin-6 (IL-6) in insulin-treated diabetic rats with or without periodontitis. Forty male Wistar rats were randomly divided into 2 groups (20 rats each): a) insulin-treated diabetic group (control, DI) and b) insulin-treated diabetic periodontitis group (test, DIP). Diabetes was induced, and insulin treatment was initiated on day 5. On day 16, periodontitis was induced in the DIP group. All rats were euthanized on day 77. Adiponectin and IL-6 were assessed on days 16 and 77. At the end of the experiment, 14 and 11 rats survived in the DI and DIP groups, respectively. Adiponectin levels were statistically significantly higher at the end of the experiment compared with levels on day 16 in the periodontitis group (p < 0.05), but not in the control group. At the end of the experiment, adiponectin levels were statistically significantly higher in the periodontitis group compared with the control group (p < 0.05). Within-group and between-group comparisons of IL-6 levels showed no statistically significant difference. In conclusion, serum adiponectin was increased in insulin-treated diabetic rats with periodontitis in comparison with insulin-treated diabetic rats, while IL-6 levels did not differ between groups.

Tissue Eosinophilia

To investigate whether tissue eosinophilia is a differentiating histopathologic feature of drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) compared with non-DI-SCLE. Retrospective medical record review with prospective blinded histopathologic analysis. University-affiliated dermatology and dermatopathology practice. Fifty-nine patients with SCLE were divided into DI (n = 15) and non-DI (n = 44) groups. A dermatopathologist masked to the etiologic associations reviewed corresponding histopathologic specimens. For each patient, an eosinophil ratio was calculated as the mean eosinophil score (averaging eosinophil counts from 10 high-power histologic fields) divided by the intensity of inflammation. Eosinophil ratios for both groups were compared using the Mann-Whitney test. No significant difference was found in mean eosinophil ratios in the DI vs non-DI groups (0.11 vs 0.004; P = .34). Mucin deposition was present in both populations and was not significantly different (P = .18). The inflammatory infiltrate was superficial and deep in 10 patients (67%) in the DI group vs 24 (55%) in the non-DI group. Periadnexal inflammation was observed in 12 patients (80%) in the DI group vs 37 (84%) in the non-DI group, and basal layer liquefaction with dyskeratosis was seen in 15 patients (100%) in the DI group and in 37 (84%) in the non-DI group. Tissue eosinophilia is not a differentiating histopathologic feature of DI-SCLE. Careful review of a patient's drug history in correlation with clinical findings remains the standard for identifying a drug as an etiologic or exacerbating factor in patients with SCLE.

Effect of vanadium on renal Na+,K+-ATPase activity in diabetic rats: a possible role of leptin

Several researches attempt to protect diabetic patients from the development of nephropathy. Involvement of leptin and renal Na+,K+-ATPase enzyme in diabetic nephropathy (DN) development is a recent field for researches. Vanadium, as a trace element with insulin mimetic effect, may act synergistically with insulin to protect against the development of DN. Sixty male Sprague Dawley rats were divided into six groups: control group (C), vanadium control group (CV), streptozotocin-induced diabetic group (D), insulin-treated diabetic group (DI), vanadium-treated diabetic group (DV), and combined insulin and vanadium-treated diabetic group. Six weeks later, systolic blood pressure (SBP) was measured and retro-orbital blood samples were collected to estimate glycosylated hemoglobin (HbA(₁c)), serum sodium (Na+) and creatinine, blood urea nitrogen (BUN) and plasma leptin levels. Preparation of microsomal fraction of renal tissue homogenate for estimation of Na+,K+-ATPase activity was done. The D group showed a significant increase in SBP, HbA(₁c), serum Na+, creatinine, and BUN levels and Na+,K+-ATPase activity in microsomal fraction of renal tissue homogenate while plasma leptin level decreased significantly compared with C and CV groups. Both DI and DV groups showed a significant improvement in all the above measured parameters compared with D group while there were no significant changes between the DI and DV groups. Concomitant treatment with insulin and vanadium resulted in a significant improvement in all the measured parameters compared to each alone. Vanadium in combination with insulin ameliorates DN markers and reduces renal Na+,K+-ATPase overactivity in diabetic rats. An effect that may be partially mediated through correction of hypoleptinemia observed in these animals.

Chronological changes in compromised olivocochlear activity and the effect of insulin in diabetic Wistar rats

The aims of the present study were to investigate in diabetic rats: (1) the chronological changes of compromised medial olivocochlear bundle (MOCB) activity and auditory brainstem responses (ABR) and (2) the effect of insulin on diabetes-related hearing dysfunction. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. Thirty male Wistar rats were divided into three groups: control (C), diabetes with insulin injection (DI), and diabetes without insulin injection (DM). Click-evoked ABR, distortion product otoacoustic emission (DPOAE) and the contralateral suppression (CS) of DPOAE were measured for all animals monthly. Throughout the experiment, the thresholds of click-evoked ABR did not differ among groups. Wave III was delayed and interpeak latency I–III was prolonged in the DM group at the age of 29 weeks ( p < 0.05). The amplitudes of the CS of DPOAE were markedly decreased after the 25th week in the DM group, but not in the C and DI groups. Compared to the C group, the CS in the DI group was not attenuated at any frequency. Dysfunction of auditory efferent olivocochlear activity developed in diabetic rats presenting no evidence of hearing loss. The finding of a significant decrease of the CS of DPOAE could be used as an earlier indicator of diabetes-related hearing impairment than changes of ABRs. The time course of compromised MOCB is positively correlated with the duration of diabetes. Insulin could therefore protect against compromised MOCB.

Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord.

Influence of Insulin and Muscle Fiber Type in Nε-(Carboxymethyl)-Lysine Accumulation in Soleus Muscle of Rats with Streptozotocin-Induced Diabetes Mellitus

Background: Nε-(carboxymethyl)-lysine (CML) is an advanced glycation end product (AGE), the accumulation of which has been implicated in the etiology of diabetes complications. Skeletal muscle in diabetes demonstrates altered function, and increased accumulation of CML has been found in several fast-twitch muscles of diabetic animals. Objective: This study aims to explore the accumulation of CML in soleus (a slow muscle) in diabetic animals, with and without insulin therapy. Methods: Twenty-one rats were randomly divided into control and diabetes groups (DNI: diabetes without insulin; DI: diabetes with insulin; C: control). Diabetes was induced by intravenous administration of streptozotocin. At the end of the 12-week experimental period the soleus muscle was excised and snap frozen in liquid nitrogen. Muscle cross-sections were immunolabeled for CML. The number of CML-labeled muscle fibers was quantified; fibers were also evaluated for fiber types and cross-sectional areas. Results: The percentage of myofibers immunolabeling for CML was highest in the DNI group (13.8 ± 2.5%), lower in the DI group (5.4 ± 1.1%) and lowest in the C group (2.1 ± 0.6%). Statistical analysis revealed that AGE accumulation was significantly greater in the DNI group than in both C and DI groups (p = 0.0002). There was no significant difference between C and DI groups. In the DNI animals, AGE-positive myofibers showed a higher percentage of fast fiber types than did the AGE-negative fibers (49.5 ± 6.9 vs. 13.7 ± 1.5%, p = 0.002). No differences existed in cross-sectional areas between AGE-positive and AGE-negative fibers within any group. Conclusion: The greatest accumulation of AGE was in the soleus of the DNI group, and was significantly less in the DI group. These findings may be linked to disordered glucose metabolism, increased oxidative stress and/or fiber type transformation in these muscles.

Different Mechanisms for the Progression of CKD with ACE Gene Polymorphisms

Background/Aims: The blockade of the renin-angiotensin-aldosterone system is the major target of efforts to prevent the progression of chronic kidney disease (CKD). Dual blockade with angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker has been reported to show additive renoprotection. However, three types of insertion/deletion (I/D) polymorphism have been reported, and it is unclear whether the dual blockade is effective for all the ACE genotypes. Methods: We treated 93 CKD patients with or without dual blockade and analyzed the effects on blood pressure (BP), proteinuria, progression of CKD and the relationship to I/D ACE polymorphisms. Results: After long-term medication (average 33 ± 2 months), BP decreased in all the genotype groups. However, urinary protein excretion decreased only in the II and DI groups (II: –27.1%, DI: –20.5%, DD: +0.8%). In the II and DI groups, amelioration of the progression of renal failure was correlated with reductions in BP and urinary protein excretion. However, the progression rate of renal failure was not correlated with proteinuria in the DD group. Conclusion: Proteinuria and BP are key factors for the progression of CKD in II/DI patients, while controlling the BP rather than reducing the proteinuria appears to be crucial in DD patients.

The dynamic balance of the children with cerebral palsy and typical developing during gait. Part I: Spatial relationship between COM and COP trajectories

Analysis of the COM or COP movement has been a simplified method to illustrate the balance disorders in static stance and gait, but has its limitation when examined alone. Dynamic stability of 32 children with cerebral palsy (CP) was examined and compared with 10 typically developing (TD) children by measuring the displacement of center of mass (COM) and center of pressure (COP) and their spatial relationship. The children with CP were further divided into two groups based on topographical involvement, hemiplegia (Hemi) and diplegia (Di). The participants walked with their preferred speed at least 5 successful trials on a walkway with two force plates mounted in the middle. An eight-camera motion analysis was used to capture 26 reflective markers secured at the bony landmarks of the participant. The data obtained from motion analysis and force plates was used to calculate COM and COP. The results showed either of two CP groups demonstrated significantly greater peak-to-peak COM and COP displacement in medio-lateral (ML) and lower peak-to-peak COM and COP displacement in anterio-posterior (AP) direction than TD group. The root mean square (RMS) of COM–COP divergence of Hemi and Di groups were higher than that of TD group in AP and ML direction, but only the difference in ML direction was significant. Present study demonstrates that COM–COP divergence can characterize the dynamic balance of the CP children in walking, and thus assist in comparing and differentiating balance patterns.

Psychosocial Predictors of Dementia Caregiver Desire to Institutionalize: Caregiver, Care Recipient, and Family Relationship Factors

Several factors influence dementia caregiver desire to institutionalize; however, little is known about differences in caregivers who desire institutionalization versus those who do not. The current study compares predictors of desire to institutionalize in dementia caregivers. Seventy-two caregivers completed the Desire to Institutionalize Scale (DIS) and several psychosocial measures, including burden, dementia knowledge, self-efficacy, depression, health, care recipient daily functioning and memory/behavior problems, family functioning, and social support. Based on DIS responses, caregivers were divided into No DI versus DI groups. DI caregivers had significantly higher burden, greater dementia knowledge, more family dysfunction, and decreased social support compared with No DI caregivers. Findings emphasize the importance of caregiver and family relationship variables in DIS, suggesting potentially modifiable targets for caregiver interventions. Dementia knowledge was associated with higher DIS, suggesting that educational programs alone may not be helpful to delay institutionalization.

Effects of Angiotensin-Converting Enzyme Polymorphism on Aortic Elastic Parameters in Athletes

Background: Physiologic adaptations in an athlete’s heart include increased left and right ventricular chamber size, left ventricular wall thickness and mass. Angiotensin-converting enzyme (ACE) is a key enzyme in angiotensin II production causing cardiac hypertrophy. The cloning of the ACE gene has made it possible to identifya deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. Therefore, the ACE genes, which have been shown to be polymorphic, could be candidate genes for large-artery stiffness. Methods: 56 endurance athletes and 46 sedentary subjects were included in this study, and they underwent both complete echocardiographic examination, and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood. The aortic diameter was recorded by M-mode echocardiography at a level 3 cm above the aortic valve. Aortic systolic diameter was measured at the time of full opening of the aortic valve, and diastolic diameter was measured at the peak of QRS. Aortic strain, stiffness index and distensibility were calculated. Results: Left ventricular mass index and left ventricular ejection fraction were significantly higher in athletes than controls (p < 0.001). The aortic distensibility index and strain were significantly greater in athletes compared with controls (respectively: 5.8 ± 2.7 vs. 4.7 ± 1.8 cm^–2 dyn^–1 10^–6, p = 0.017; 12.3 ± 2.4 vs. 9.3 ± 3.1, p < 0.001). The aortic stiffness index was significantly lower in athletes than in controls (4.8 ± 1.9 vs. 6.1 ± 2.1, p < 0.001). The aortic distensibility index and strain were statistically different in ACE DD vs. DI groups and DD vs. II groups of athletes. The aortic stiffness index was statistically different in ACE DD vs. II groups of athletes. Aortic parameters were similar according to ACE genotypes in controls. Conclusion: The results of this study indicate that aortic distensibility was increased by prolonged training in endurance athletes, particularly in those with the ACE II genotype. This effect represents an extracardiac adaptation to chronic prolonged training in athletes.

Comparison of a combination of midazolam and diazepam and midazolam alone as oral premedication on preanesthetic and emergence condition in children

Preanesthetic anxiety and emergence agitation are major challenges for anesthesiologists in pediatric anesthesia. Thus, midazolam has been used as premedication for children. However, midazolam alone is not effective for emergence agitation. The present study tested the effect of a combination of midazolam and diazepam on the preanesthetic condition and emergence behavior in children. Forty-two children were allocated to one of three groups: the NoPre group received no premedication; the Mi group received midazolam 0.5 mg kg(-1) orally; and the Mi + Di group received midazolam 0.25 mg kg(-1) and diazepam 0.25 mg kg(-1) orally. When anesthesia was induced with 7% sevoflurane in 100% oxygen, qualities of mask induction and sedation were rated. Anesthesia was maintained with sevoflurane (3-5%) in 100% oxygen. During emergence from anesthesia, the score of the child's emergence behavior was rated. Children in the Mi and Mi + Di groups were more sedated than those in the NoPre group. A combination of midazolam and diazepam provided a better quality of mask induction, when compared with no premedication. Also, the children in the Mi + Di group were less agitated than those in the other groups during the emergence. Children in the Mi + Di group were significantly more sedated at induction of anesthesia and less agitated during emergence from anesthesia.

Effects of insulin on renal interstitial hydrostatic pressure and natriuretic response to volume expansion in diabetic rats

Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FE(Na)), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (Delta RIHP), and FE(Na) and V responses to VE (Delta FE(Na) and Delta V) were significantly lower in the D group compared with the C group of rats. Delta RIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the Delta FE(Na) response to VE was restored, Delta FE(Na) was significantly increased in DDI compared with D group, but it remained lower than that of the C group. In conclusion, insulin treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.

In vivo antidiabetic actions of naglivan, an organic vanadyl compound in streptozotocin-induced diabetes

The vanadyl (+IV) form of vanadium has been demonstrated to have insulin-mimetic activity in vivo. In an effort to improve the poor gastrointestinal absorption of the ion, an organic complex of vanadyl (naglivan) was synthesized. We tested the antidiabetic effects of naglivan in rats made diabetic with streptozotocin (55 mg/kg, i.v.). Four days after the streptozotocin injection, one diabetic group (DVI) and a control group (CV) were treated with naglivan (50 mg/kg/day, equivalent to 0.06 mmol vanadium/kg/day) by oral gavage. Treatment in the DVI group was supplemented with daily insulin while a second diabetic group (DI) was administered daily titrated doses of insulin alone (Protamine Zinc, s.c.) to achieve stable euglycemia. The dose of exogenous insulin required to maintain normal glucose was significantly lower in the DVI group compared to the DI throughout the treatment period. At the end of week 3, exogenous insulin was withdrawn from both the DVI and DI groups, while naglivan treatment was continued in the CV and DVI groups for an additional 5 weeks. At termination, hearts were isolated and cardiac function ( +dP dt , −dP dt and left ventricular developed pressure) was assessed in all the animals. After insulin was withdrawn, 4 8 DVI animals which continued to receive naglivan had consistent normoglycemia (as determined by % glycosylated hemoglobin) and an improved cardiac function. All the DI animals and 4 8 DVI rats were hyperglycemic and had depressed heart function despite having similar plasma insulin levels to the euglycemic DVI animals. As with vanadyl sulfate, there were no signs of long-term toxicity with regards to renal or liver function after 8 weeks of treatment. Thus, naglivan is an orally effective form of vanadyl with an oral potency 7.6 times greater than that of vanadyl sulfate (minimum effective dose: 0.06 mmol vanadium·kg −1·day −1) as compared to vanadyl sulfate (0.46 mmol vanadium·kg −1·day −1). The lack of incidence of diarrhea in either control or diabetic animals demonstrates that naglivan could be a more therapeutically desirable form of vanadyl.

Diagnostic significance of urinary sialic acid in diabetic nephropathy.

The diagnostic significance of urinary sialic acid (SA) determinations was evaluated in relation to the histological findings of renal biopsy specimens. The subjects enrolled in this study comprised 82 diabetics. They were divided into 4 groups according to Gellman's criteria, namely D0, DI, DII and DIII approximately IV. Thirty non-diabetic healthy volunteers were used as controls. The urinary SA was measured by high performance liquid chromatography, and the urinary albumin excretion was estimated by solid phase radioimmunoassay. In addition, urine samples were assayed for N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (beta 2MG). The urinary level of total SA (under conditions of hydrolysis) was significantly increased in the DII and DIII approximately IV groups as compared to the controls; however, a similar value was observed in the D0, DI and control groups. The urinary level of glycoprotein-bound SA was significantly increased in all diabetics as compared to the control group, and was significantly higher in the DII and DIII approximately IV groups than in the D0 and DI groups. The bound-SA/total-SA ratio (B/T ratio) showed a significant increase with respect to the progress of diffuse lesions. A weak correlation was noted between the B/T ratio and urinary protein excretion. However, there was no correlation between the B/T ratio and other indices. The urinary SA is considered to represent a useful indicator for estimating diabetic nephropathy.

The Hypothalamic-Pituitary Axis of Streptozotocin-Induced Diabetic Female Rats is Not Normalized by Estradiol Replacement*

Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary, and/or ovarian level but have not controlled for changes in estrogen levels induced by diabetes. The purpose of this investigation was to study the effect of diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with estradiol (E2). Ovariectomized 60 day old female rats were assigned to control (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16) groups. Diabetes was induced with an injection of streptozotocin in the D and DI groups. In the C, D, and DI groups, estrogen was replaced by implanting blank, 5 micrograms or 20 micrograms E2 pellets sc. Pituitary LH responsiveness to GnRH was assessed in C and D animals. Anterior hypothalamic and midhypothalamic concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH, and E2 were measured by RIA. Anterior hypothalamic proGnRH concentrations were decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms E2 control animals (P less than 0.05). Midhypothalamic GnRH concentrations were also reduced in D vs. C animals despite comparable estrogen therapy (P less than 0.004). GnRH-stimulated LH levels were greater in E2-treated diabetic females than in similarly treated control rats (P less than 0.001). D and DI animals were more sensitive than controls to the inhibitory effect of estrogen on basal LH levels. Pituitary LH and FSH content was lower in 20 micrograms E2-replaced animals but was not influenced by the diabetic state. These data demonstrate a diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is not corrected with E2 replacement. The hyper-responsiveness of the diabetic rat pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the hypothalamus but a continued ability of the pituitary to respond to GnRH.