Effects of testosterone enanthate and resistance training on myocardium in Wistar rats; clinical and anatomical pathology.

This study was performed to determine the effects of 8 weeks testosterone enanthate (TE) injection and resistance training (RT) on cardiac muscle in male Wistar rats. A total of 28 male adult Wistar rats were randomly divided into 4 groups; control + placebo, RT + placebo, TE and TE + RT. Testosterone enanthate (20 mg/kg BW, IM) and placebo (olive oil; 0.2 ml, IM) were injected twice a week for 2 months. The RT consisted of climbing (5 reps/3 sets) a ladder carrying a load suspended from the tail. The serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) and serum level of creatinine, urea and cardiac troponin I (CTnI) were evaluated. After sacrifice, samples from myocardial muscle were collected for histopathology evaluation. The serum concentration of CTnI and CK-MB activity significantly increased in group RT compared with control (p < .05). In group RT + TE, all biomarkers of muscle damage (CTnI, CK-MB, AST, LDH) were significantly more than those in control (p < .05). Also, mild myocardial hypertrophy was observed in RT and RT + TE groups. The higher level of all heart damage biomarkers in the RT + TE group rather than control may indicate the synergistic effects of medication and exercise.

Oxidant/antioxidant status in cattle with liver cystic echinococcosis.

The objective of the present study was to evaluate the changes of antioxidants and oxidative stress markers in cattle with cystic echinococcosis (CE). Thirty cattle with liver CE along with 30 healthy cattle were used for the study. Parasitized cattle presented a significantly higher lipid peroxidation assessed by the malondialdehyde (MDA) compared with healthy animals (P<0.05). A significantly lower erythrocyte superoxide dismutase (SOD) and glucose 6-phosphate dehydrogenase (G6PD), and a significantly higher erythrocyte glutathione peroxidase (GPx) in the parasitized group, were observed when compared with healthy group (P<0.05). No significant differences were observed for serum total antioxidant status (TAS), zinc, copper and iron between parasitized and healthy groups. The results obtained in this study suggest that CE in cattle induces changes in the activity of antioxidant enzymes. These changes render host cells susceptible to oxidants and exaggerate the generation of free radicals with a consequent lipid peroxidation enhancement.

Oxidative stress and trace elements in camel (Camelus dromedarius) with liver cystic echinococcosis.

Status of certain oxidative stress indices and zinc, copper and iron concentrations in blood were estimated in camel with liver cystic echinococcosis. In comparison to healthy control, the index of serum lipid peroxidation assessed by the malondialdehyde (MDA) level was significantly higher in the parasitized group. However, mean serum total antioxidant status (TAS) and erythrocyte glutathione peroxidase (GPx) were significantly lower in the parasitized group. Serum zinc concentration in camels with liver cystic echinococcosis was significantly lower than healthy control. In parasitized camels, a significant positive correlation of MDA with gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and bilirubin was observed. By contrast, MDA was inversely correlated with the values of packed cell volume (PCV), serum albumin and zinc. From the present study, it was concluded that cystic echinococcosis in camel is associated with oxidative stress. The resulting oxidative stress seems to have a role in the injury of hepatocytes, changes of trace elements and destruction of erythrocytes.

Comparison of the effects of gonadotropin-releasing hormone, human chorionic gonadotropin or progesterone on pregnancy per artificial insemination in repeat-breeder dairy cows.

Three different treatments were compared to improve pregnancy per artificial insemination (P/AI) in repeat-breeder (RB) dairy cows. All cows (n=103) were assigned to one of four groups: (1) gonadotropin-releasing hormone (GnRH); (2) human chorionic gonadotropin (hCG); (3) once-used controlled internal drug release (CIDR) device; and (4) control. All treatments performed 5-6days after artificial insemination (AI) and milk samples were collected just before treatment for progesterone assays. There were no significant differences in milk fat progesterone concentration among trial groups. Cows were observed for estrus signs thrice daily. Pregnancy per AI on day 45 in hCG and CIDR groups were significantly higher than GnRH and control groups (60.0% and 56.0% vs. 26.9% and 29.6%, respectively), but there were no differences in P/AI between GnRH and control groups. There were also no significant differences between hCG and CIDR groups. Milk fat progesterone concentrations were compared between pregnant and non-pregnant cows in each group and only in the hCG group it was significantly lower in pregnant cows. In conclusion, treating repeat-breeder cows with hCG or once-used CIDR 5-6days after AI improved P/AI.

Effects of parenteral supply of iron and copper on hematology, weight gain, and health in neonatal dairy calves.

The objective of the present study was to examine the effects of parenteral administration of iron and copper on hematological parameters, weight gain, and health of neonatal dairy calves in the period when iron and copper deficiency could be existed. Twenty-four Holstein calves were used for the experiment and randomly assigned to four different treatments. Treatments consisted of (1) control (no injections of Fe and Cu), (2) test 1 (1000 mg Fe as fe-dextran was injected to each calf at day 2 of age), (3) test 2 (160 mg Cu as methionine-copper complex was injected to each calf at day 14 of age), and (4) test 3 (Fe and Cu were injected to each calf as mentioned previously). Blood samples were collected from all of the calves within 24-48 hours after birth and at 7, 14, 21 and 28 days of age for measuring hematological parameters and within 24-48 hours after birth and at 14, 21 and 28 days of age for the determination of iron, copper, TIBC concentrations, and AST activity. Anti-coagulated blood was analyzed shortly after collection for: number of red blood cell (RBC), hemoglobin (Hb), heamatocrit (HCT), total leukocyte count (WBC), Platelet (Plt), MCH, MCV, MCHC, and differential leukocyte counts. The amounts of iron, copper, TIBC, and AST were measured in serum. Group had significant effects on the amounts of HCT, RBC, hemoglobin, MCV, neutrophil, weekly weight gain, and daily gain during each week (p < 0.05). Sampling time had significant effects on the amounts of RBC, MCV, MCH, MCHC, WBC, neutrophil, lymphocyte, monocyte, platelet, fibrinogen, copper, TIBC, AST, weight, weekly gain and, daily gain during each week (p < 0.05). significant interactions between sampling time and group were seen for HCT, RBC, hemoglobin, MCV, platelet, total protein, fibrinogen, iron, and TIBC (p < 0.05). Improved RBC parameters and MCV were seen in calves of group 4 (test 3) in comparing with control group. Total and daily gains were also significantly improved in test groups in comparing with control group (p < 0.05). No significant difference was seen for the days of treatment between groups.

The relationship between normocytic, hypochromic anaemia and iron concentration together with hepatic enzyme activities in cattle infected with Fasciola hepatica.

Erythrograms determined from whole blood analyses and serum analyses for aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) activities, and iron concentration, were used in infected and uninfected cattle to determine the type of anaemia and degree of hepatic damage caused by Fasciola hepatica. Blood samples from 86 infected and 30 uninfected cattle were taken at slaughter. Haematological analyses revealed decreased levels of packed cell volume (PCV), haemoglobin concentration, mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) in infected compared with uninfected cattle (P < 0.05). A decrease in the concentration of serum iron was also observed in infected cattle compared with uninfected cattle (P < 0.05). Significant increases in AST, GGT and ALP activities were observed in cattle infected with F. hepatica when compared with uninfected cattle (P < 0.05). It was concluded that the anaemia observed in cattle infected with F. hepatica is a normocytic, hypochromic anaemia and the most important aetiology of the anaemia is the chronic blood loss due to the blood-sucking activity of the adult flukes and leakage of blood from the bile duct to the intestine, which results in iron deficiency. The increased activities of serum enzymes indicated chronic hepatic and bile duct injuries associated with chronic infection with F. hepatica.

Studies on haemoglobin polymorphism of two breeds of Iranian sheep and its relationship to concentrations of iron, copper, haemoglobin, haematocrit and RBC number.

After electrophoresis on cellulose acetate, two haemoglobin phenotypes were detected in Baloochi and Kordi breeds: AA and AB phenotypes. AA was commonest in two breeds. The incidence of type AB haemoglobin in Baloochi and Kordi breeds was 26.5% (9/34) and 9.5% (2/21), respectively. BB phenotype was not seen in Baloochi and Kordi breeds. In sheep with AB phenotype, haemoglobin B was dominant. The mean +/- SD of the two kinds of haemoglobin in sheep with AB phenotype were haemoglobin B percentage 60.5% +/- 9.04%, haemoglobin B absolute 73.84 +/- 5.44 g/L, haemoglobin A percentage 39.5% +/- 9.04%, haemoglobin A absolute 32.88 +/- 2.89 g/L. There were no significant differences for total haemoglobin, haematocrit, red blood cell (RBC) number, iron and copper levels between breed, sex and age groups and also between sheep with AA phenotype and AB phenotype. Pearson's method showed significant correlations for total haemoglobin with packed cell volume (PCV), RBC number, copper concentration and RBC number with PCV, copper level and PCV with copper amount and copper concentration with iron level (p<0.05). In the Kordi breed, significant correlations were seen for total haemoglobin with PCV, RBC number, copper concentration and PCV with RBC number and RBC number with copper level and copper concentration with iron amount (p<0.05). In the Baloochi breed, significant correlations were detected for total haemoglobin with PCV, RBC number and PCV with RBC number (p<0.05).

Phase I study of a novel recombinant human soluble thrombomodulin, ART-123.

BACKGROUND: Anticoagulants are often given for extended periods of time to patients at high risk for venous thromboembolism, such as after orthopedic surgery. Daily subcutaneous (sc) injections can be inconvenient to the patient. A long-acting anticoagulant requiring less frequent dosing could make treatment more acceptable. Thrombomodulin is a natural anticoagulant that activates protein C, which leads to inactivation of factor (F)Va and FVIIIa and decreased thrombin formation. Recombinant human thrombomodulin is a novel anticoagulant with a long half-life in animal models. METHODS AND RESULTS: This phase I study examined pharmacokinetics, pharmacodynamics, and safety of recombinant human soluble thrombomodulin (ART-123) after administration of doses between 0.02 and 0.06 mg kg(-1) body weight intravenously (iv), and between 0.02 and 0.45 mg kg(-1) sc in 55 healthy volunteers. The plasma half-life was 2-3 days after sc injection of various single doses. Plasma ART-123 levels estimated to be needed for prevention of thrombus formation in humans were maintained for at least 6 days after single sc injection of 0.30 and 0.45 mg kg(-1) ART-123. Antithrombotic activity with these doses was demonstrated by achieving prothrombinase inhibition of more than 80% for more than 6 days after administration. No major bleeding occurred. Pharmacodynamic modeling revealed that adequate antithrombotic ART-123 levels can be achieved for 6 days with one dose of 0.45 mg kg(-1) ART-123, and for 12 days with 2 doses of 0.30 mg kg(-1), given 5 days apart. CONCLUSIONS: Recombinant human soluble thrombomodulin (ART-123) has a long half-life after sc injection and is well tolerated, making it a suitable agent to be tested in clinical thromboprophylaxis trials.

Outbreak of osteodystrophia fibrosa in young goats.

Osteodystrophia fibrosa was diagnosed in young goats which received a dict of 60% wheat straw and 40% barley for 8 months. The ratio of calcium:phosphorus in the diet was 1:1.8. The clinical signs were bilateral and symmetrical enlargement of the face, swelling of the joints, and limb deformities. The laboratory findings showed a low level of serum calcium in all affected goats. Histopathological examination revealed marked fibrous deposition and osteoclasia in bones of the maxilla and mandible.

Acyclovir improves recovery rate of facial nerve palsy in Ramsay Hunt syndrome.

OBJECTIVE: Although the antiviral agent, acyclovir, is currently employed for the treatment in Ramsay Hunt syndrome, the benefit of acyclovir on facial nerve is still unknown and remains controversial. This study was designed to evaluate the effect of acyclovir in facial nerve recovery in Ramsay Hunt syndrome. METHODS: To evaluate drug effect on facial nerve function, evaluation of the facial voluntary movement and nerve excitability testing were performed. We have used an infusion therapy of acyclovir in combination with a high dose of steroid (AS), which was started within 7 days of onset of facial nerve palsy in 91 patients with Ramsay Hunt syndrome. The results were compared with those of 47 patients whose therapy was steroid alone started within 7 days of onset. RESULTS: Out of 91 patients treated with AS, nerve exitability was good in 68 (75%), while it was poor in 17 and absent in six. Of 47 patients treated with steroid alone, nerve exitability was good in 25 (53%), while it was poor in 11 and absent in 11. There was statistically significant difference between AS and steroid therapy in the posttreatment degree of nerve function. Complete recovery to grade I in facial voluntary movement was attained in 82 of 91 patients (90%) in the AS therapy, while out of 47 patients treated with steroid alone complete recovery to grade I was attained in only 30 (64%). A statistically significant difference in the recovery rate of facial nerve function was induced between AS and steroid therapy. CONCLUSION: The AS therapy was proved to keep good degree of nerve function indicated with nerve excitability testing and improve recovery rate of facial nerve in Ramsay Hunt syndrome. Based on this study, we now believe that the AS therapy is an advisable treatment modality to improve the recovery rate of facial nerve function in Ramsay Hunt syndrome.

Role of hypertension, dyslipidemia and diabetes mellitus in the development of coronary atherosclerosis in Japan.

The present study evaluated the effect of hypertension (HT), dyslipidemia and diabetes mellitus (DM) on the development of coronary atherosclerosis in the Japanese population, using a cross-sectional study of 433 patients (254 men and 179 women) aged 30 years or older who underwent coronary angiography for suspected or known coronary heart disease angina at 5 cardiology departments in the Fukuoka area between September 1996 and August 1997. Patients with a disease duration of 6 months or more were excluded. The main outcome measure was angiographically defined coronary artery stenosis and was found to a significant degree in 146 patients (33.7%). HT, DM, low levels of high-density lipoprotein cholesterol (HDL-C) and hypertriglyceridemia remained as significant coronary artery disease (CAD) risk factors even after controlling for age, sex, hospital, smoking, alcohol use, body mass index and leisure time physical activity. However, hypercholesterolemia was not a significant risk factor after adjusting for these variables. After controlling for these variables, DM, low HDL-C and hypertriglyceridemia were significant CAD risk factors for men, but only DM was a significant CAD risk factor in women. These results indicate that in Japan DM, low HDL-C and hypertriglyceridemia may be more important CAD risk factors than hypercholesterolemia.

Significance of retropharyngeal node dissection at radical surgery for carcinoma of the hypopharynx and cervical esophagus.

OBJECTIVES: To clarify the efficacy of dissection of retropharyngeal lymph nodes (RPLNs) in the surgical treatment of carcinoma of the hypopharynx and cervical esophagus. STUDY DESIGN: We started planned dissection of the RPLN during initial radical surgery in patients with squamous cell carcinoma of the hypopharynx or the cervical esophagus in 1988. Until 1997, we performed this procedure as a standard operation in 82 consecutive patients. METHODS: Mortality resulting from RPLN metastasis was compared between 82 patients who underwent RPLN dissection and 69 patients who did not undergo the procedure. RESULTS: Of 82 patients, 16 patients (20%) had positive RPLNs. These patients were at high risk of recurrence unless the node(s) were dissected. Although RPLN dissection did not improve the cumulative 5-year survival rate, it significantly decreased the number of patients who died of RPLN metastasis (chi2 = 3.68, P <.1). Four of the 16 patients who had positive RPLNs survived without any recurrence. CONCLUSION: Bilateral dissection of the RPLN during initial surgery is highly recommended in every surgical case of carcinoma of the hypopharynx and cervical esophagus.

Posttransplant function of a nonbeating heart is predictable by an ex vivo perfusion method.

BACKGROUND: We attempted to predict the posttransplant cardiac function of nonbeating donor hearts. METHODS: A total of 13 dogs were studied. Hearts were left in situ for 45 minutes after cardiac arrest caused by exsanguination. Hearts were then excised and reperfused in an ex vivo perfusion apparatus after 60 minutes of warm ischemia to test whether they could eject against an 80 mm Hg afterload from a preload of 10 mm Hg. Thereafter, all hearts were transplanted orthotopically. RESULTS: Four of 13 hearts were able to eject in the apparatus (group A). However, the other nine hearts could not eject under the defined conditions (group B). All four hearts in group A showed good posttransplant hemodynamics (systolic arterial pressure > 80 mm Hg with mean left atrial pressure < 10 mm Hg) without dopamine. However, none of nine hearts in group B could support the circulation without dopamine. CONCLUSIONS: Nonbeating donor heart function evaluated in the perfusion apparatus predicts posttransplant heart function. This method may be applicable for selection of transplantable hearts from nonbeating heart donors.

Adrenomedullin receptors in rat choroid plexus.

To characterize transmembrane signaling of adrenomedullin (AM) in the choroid plexus, we studied the effects of AM on cyclic AMP (cAMP) and cyclic GMP (cGMP) levels as well as expression of mRNA for AM receptor in the rat choroid plexus slices. AM or calcitonin gene-related peptide (CGRP) increased cAMP (but not cGMP) level in a concentration-dependent manner, with AM being much more potently than CGRP. AM mRNA as well as calcitonin-receptor-like receptor mRNA and receptor-activity-modifying protein 2 mRNA, were highly expressed in the choroid plexus. Our biochemical and pharmacological studies may raise the possibility that choroid plexus secretes AM into the cerebrospinal fluid, and AM regulates choroid plexus function in an autocrine/paracrine manner via acting on AM-specific receptors.

Adrenomedullin receptors in rat cerebral microvessels.

To characterize the sites of action of adrenomedullin (AM) in the cerebral microvasculature, we studied the effect of AM on cyclic AMP (cAMP) level as well as expression of AM and its receptor in the rat cerebral microvessels. The microvessels were prepared from rat cerebral cortex by albumin flotation and glass bead filtration technique. AM and calcitonin gene-related peptide (CGRP) increased cAMP level in the microvessels in a concentration-dependent manner. The effect of AM was more than 100 times more potent than that of CGRP. The accumulation of cAMP by AM was inhibited by AM[22-52], an AM receptor antagonist, but not by CGRP[8-37], a CGRP receptor antagonist, suggesting that AM increased cAMP accumulation by acting on receptors specific to AM. [125I]AM binding to the microvessels was displaced by AM and less potently by AM[22-52]. The displacing potencies of CGRP and CGRP[8-37] were very weak. mRNAs for AM as well as calcitonin-receptor-like receptor and receptor-activity-modifying protein 2 which form a receptor specific to AM, were highly expressed in the microvessels. These results provide biochemical and pharmacological evidence that AM is produced in and acts on the cerebral microvessels in an autocrine/paracrine manner and is involved in regulation of cerebral microcirculation.

[Combined valvular and coronary artery surgery].

Between 1990 and 1999, 78 patients underwent combined valvular coronary artery operation. Aortic valve disease was present in 49 patients, mitral valve disease in 23 patients, aortic and mitral valve disease in 6 patients. The average age was 67 years. Twelve patients had had a previous myocardial infarction. The average number of grafts inserted was 1.82 per patients, and the average number of artery grafts inserted was 0.96 per patients. The most number of grafts were placed prior to valve replacement or plasty. And periods of myocardial ischemia were kept at a minimum by coronary perfusion through free grafts. Preoperative mortality was 1.3%. And event fee ratio after operation was 95% (mean follow up 42 month). Therefore the operative risk of combined surgery is, in general, low and the long term results are favorable.

Congenital defects of the vomer.

Six cases of congenital defect of the vomer, a rare nasal anomaly, are reported. All 6 patients visited Kobe University Hospital with other complaints, and the anomaly was incidentally detected. In all cases, the nasal septum showed a defect at the posteroinferior portion that appeared to coincide with the location of the vomer. None of the patients had a past history of nasal trauma, nasal surgery, drug abuse, or infectious disease. This anomaly may be attributable to an embryological disorder based on an immature ossification center of the vomer.

Expression of multidrug resistance-associated protein (MRP) in human gliomas.

Drug resistance is a major clinical problem in the chemotherapy of human gliomas. The multidrug resistance-associated protein (MRP), a membrane transporter related to non-P-glycoprotein multidrug resistance, is overexpressed in some drug-selected cancer cell lines. To investigate whether MRP is involved in the intrinsic drug resistance of human gliomas, surgical specimens of 20 gliomas (11 glioblastomas, 6 anaplastic astrocytomas, and 3 astrocytomas), 3 normal brain specimens, and 4 glioma cell lines (U87MG, U251MG, U373MG, and T98G) were analyzed. The expression of MRP was studied by RT-PCR and immunohistochemistry in the surgical specimens. The MRP expression levels in the cell lines were assessed by the quantitative RT-PCR and Western blot analyses. Sensitivity to adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), were determined by MTT assay, and antisense treatment was evaluated in the cell lines. The expression of MRP was detected in 9 of 11 glioblastomas and 3 of 6 anaplastic astrocytomas. The quantitative analyses of the cell lines revealed that the MRP mRNA and protein levels were increased 4.5-fold in the T98G cells as compared to U87MG. T98G cells showed the highest resistance to all drugs. Western blot analysis revealed that treatment with the antisense oligonucleotide reduced the level of MRP expression to 25% of the sense oligonucleotide treatment in T98G cells. The sensitivity to ADM, VP-16 and CDDP was significantly increased in the antisense-treated cells as compared with the sense-treated cells. These results suggest that the MRP expression may be related to the intrinsic multidrug resistance in human gliomas.

The effect of graft perfusion with warm blood cardioplegia for cadaver heart transplantation.

This study was designed to verify the effect of reperfusion of donor hearts in a perfusion apparatus after 60 min of global ischemia prior to heart transplantation. Thirteen dogs were exsanguinated from the femoral artery and cardiac arrest was achieved. The hearts were left in situ at room temperature (25 degrees C) for 60 min. In group A (n = 7), the hearts were excised and reperfused 60 min after cardiac arrest in the perfusion apparatus with substrate-enriched warm blood cardioplegia (WBCP) containing a hydroxyl radical scavenger, EPC, followed by 45 min of blood perfusion. Next, the hearts were preserved in cold (4 degrees C) University of Wisconsin (UW) solution. In group B (n = 6), the hearts were perfused with cold (4 degrees C) St. Thomas' solution 60 min after cardiac arrest and preserved in cold UW solution. Thereafter, all hearts in both groups were transplanted orthotopically to recipient dogs. In group A, 6 of 7 dogs were weaned from cardiopulmonary bypass (CPB). In group B, only 2 of 6 dogs were weaned from CPB. Moreover, 3 of the 6 hearts in group B did not start beating after transplantation (stone heart). This study suggested reperfusion of the donor heart in the perfusion apparatus with WBCP to be a beneficial preconditioning method when utilizing 60-min arrested hearts for transplantation.