Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice

Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 8, are B40 congeners with different lipophilicities, each less than their B80 congener, copper (II) meso-5,10,15,20-tetrakis[m-(3,5-di-o-carboranylmethoxybenzyloxy)phenyl]porphyrin, 18. Two days after the last of a series of i.p. injections in BALB/c mice bearing EMT-6 mammary tumors, a dose of 185 mg/kg 6 (54 mg/kg B) delivered over 3.5 times the concentration of boron to tumor (169 microg/g B) than did 118 mg/kg 8 (36 mg/kg B), which delivered 35 microg/g B, or 87 mg/kg 18 (30 mg/kg B), which delivered 46 microg/g B. The tumor-to-blood and tumor-to-brain boron concentration ratios at that time for all three porphyrins exceeded 80:1. Two days after the last injection, there resulted moderate thrombocytopenia that essentially disappeared two days later from 6 and 18, and mild leukocytosis from 6, 8, and 18, all of which were clinically inconsequential. Thus, 6 may rank among the most clinically promising carboranyl porphyrins ever made to deliver 10B to tumors for boron neutron-capture therapy (BNCT) that has also been tested for its toxicity in vivo.     

Syntheses and preliminary biological studies of four meso-Tetra[(nido-carboranylmethyl)phenyl]porphyrins

Two meso-tetra[(nido-carboranylmethyl)phenyl]porphyrins (para- and meta-regioisomers) and their corresponding Zn(II) complexes have been synthesized with the aim of studying the effect of carborane distribution and metalation on the biological properties of this series of compounds. In vitro cell toxicity, uptake/efflux, and subcellular localization using rat 9L, mouse B16 and/or human U-373MG cells were evaluated. All four amphiphilic porphyrins display very low cytotoxicities and time- and concentration-dependent uptake by cells, which is influenced by serum proteins. Preliminary subcellular localization studies suggest that one of these compounds localizes in close proximity to the cell nucleus. All four nido-carboranylporphyrins show promise as boron-carriers for the boron neutron capture therapy of cancers, particularly the metal-free nido-carboranylporphyrins 5 and 12, which are able to deliver higher amount of boron to cells in vitro than the corresponding zinc complexes.     

The effects of boron neutron capture irradiation on oral mucosa: evaluation using a rat tongue model.

The ventral surface of the tongue of male Fisher 344 rats was used to evaluate the response of oral mucosa to boron neutron capture irradiation. Three hours after i.p. injection of 700 mg/kg of the boron delivery agent p-boronophenylalanine (BPA), the boron concentrations in blood and tongue mucosal epithelium were approximately 21 and 23 microgram (10)B/g, respectively. The doses required to produce a 50% incidence of ulceration with X rays, the Brookhaven Medical Research Reactor thermal neutron beam alone, or the thermal neutron beam in the presence of BPA were 13.4 +/- 0.2, 4. 2 +/- 0.1, and 3.0 +/- 0.1 Gy, respectively. Ulceration of the tongue was evident by 6 to 7 days after irradiation, irrespective of the irradiation modality; healing was related to dose and was relatively rapid (相似文献   

Long-term infusions of p-boronophenylalanine for boron neutron capture therapy: evaluation using rat brain tumor and spinal cord models

Rat 9L gliosarcoma cells infiltrating the normal brain have been shown previously to accumulate only approximately 30% as much boron as the intact tumor after administration of the boronated amino acid p-boronophenylalanine (BPA). Long-term i.v. infusions of BPA were shown previously to increase the boron content of these infiltrating tumor cells significantly. Experiments to determine whether this improved BPA distribution into infiltrating tumor cells after a long-term i.v. infusion improves tumor control after BNCT in this brain tumor model and whether it has any deleterious effects in the response of the rat spinal cord to BNCT are the subjects of the present report. BPA was administered in a fructose solution at a dose of 650 mg BPA/kg by single i.p. injection or by i.v. infusion for 2 h or 6 h, at 330 mg BPA/kg h(-1). At 1 h after the end of either the 2-h or the 6-h infusion, the CNS:blood (10)B partition ratio was 0.9:1. At 3 h after the single i.p. injection, the ratio was 0.6:1. After spinal cord irradiations, the ED(50) for myeloparesis was 14.7 +/- 0.4 Gy after i.p. administration of BPA and 12.9 +/- 0.3 Gy in rats irradiated after a 6-h i.v. infusion of BPA; these values were significantly different (P < 0.001). After irradiation with 100 kVp X rays, the ED(50) was 18.6 +/- 0.1 Gy. The boron compound biological effectiveness (CBE) factors calculated for the boron neutron capture dose component were 1.2 +/- 0.1 for the i.p. BPA administration protocol and 1.5 +/- 0.1 after irradiation using the 6-h i.v. BPA infusion protocol (P < 0.05). In the rat 9L gliosarcoma brain tumor model, the blood boron concentrations at 1 h after the end of the 2-h infusion (330 mg BPA/kg h(-1); n = 15) or after the 6-h infusion (190 mg BPA/kg h(-1); n = 13) were 18.9 +/- 2.2 microg 10B/g and 20.7 +/- 1.8 microg 10B/g, respectively. The irradiation times were adjusted individually, based on the preirradiation blood sample, to deliver a predicted 50% tumor control dose of 8.2 Gy ( approximately 30 photon-equivalent Gy) to all tumors. In the present study, the long-term survival was approximately 50% and was not significantly different between the 2-h and the 6-h infusion groups. The mode of BPA administration and the time between administration and irradiation influence the 10B partition ratio between the CNS and the blood, which in turn influences the measured CBE factor. These findings underline the need for clinical biodistribution studies to be carried out to establish 10B partition ratios as a key component in the evaluation of modified administration protocols involving BPA.     

Thyroliberin injected into pregnant heifers increase birthweight and stimulate postnatal growth of calves

Birthweight (51 +/- 2 kg) and mean daily weight gain (1,306 +/- 77 g; measured during the first 120 days of postnatal life) in 8 male calves born from eight primiparous heifers (mated with the same bull) given subcutaneous TRH injections (25 micrograms/kg body wt) on days 230, 240, 250 and 265 of gestation were significantly higher (+10%) than those measured in 7 control male calves born from the same bull (47 +/- 1 kg and 1147 +/- 89 g, respectively). TRH treatment also significantly increased plasma IGF1 concentrations both in term cows and in newborn calves.     

Stimulation of vascular Na-K pump with subpressor angiotensin II in rats.

The effect of subpressor doses of angiotensin II (ANG II) on vascular Na-K pump activity and Na-H exchange, two transmembrane signals of trophic stimulation of vascular muscle, was investigated. Male Sprague-Dawley rats (350-400 g) were given subpressor doses of ANG II by osmotic minipump intraperitoneally for 24 hr or 7-10 days. Control rats received sham procedure/vehicle infusion. Na-K pump activity (86Rb uptake), total and intracellular (Li exchange at 4 degrees C) Na content, and amiloride-sensitive and -insensitive Na uptake of aortas were measured ex vivo. Ouabain-sensitive 86Rb uptake of aortas of rats receiving 80-100, 160-180, and 240-260 ng/kg.min-1 of ANG II for 24 hr was 26.6 +/- 3.5, 28.8 +/- 3.4, and 29.1 +/- 2.6 nmol/mg dry wt.15 min-1 (mean +/- SD, n = 7-12), respectively, compared with 25.2 +/- 3.8 in controls (n = 23, P less than 0.01). These increases were maintained at 7-10 days. After 24 hr and 7-10 days of ANG II treatment, the total Na content of aortas was increased by 9.2% (P less than 0.01) and 7.6% (P less than 0.02), respectively, without a change in intracellular Na content, indicating accumulation of excess extracellular Na. Total and amiloride-sensitive Na uptake of the aorta was unchanged after 24 hr or 7-10 days of ANG II administration. The dry weight of anatomically defined segments of the aorta was 40 +/- 3.8 mg/kg body wt (n = 25) after 24 hr and 42 +/- 4.4 (n = 20) after 7-10 days of ANG II administration, compared with 37 +/- 4.8 (n = 15, P less than 0.05) and 37 +/- 4.9 (n = 17, P less than 0.01) in appropriate controls. Increased Na-K pump activity may signal the onset of trophic stimulation of vascular muscle by ANG II.     

Effect of type and quantity of concentrates on superovulation and embryo yield in beef heifers

Embryo yield and quality can be decreased following superovulation of cattle on high levels of concentrates. Concentrate type can alter rumen fermentation patterns and so affect energy availability and thus embryo quality. The objectives of this experiment were to examine the effect of 2 levels and 2 types of concentrate on superovulatory response and embryo quality in beef heifers. Beef heifers received grass silage as a basal diet and barley at 3 kg (n = 20) or ad-libitum (n = 19), or citrus/beet pulp at 3 kg (n = 18) or ad-libitum (n = 19) as the source of concentrate supplement. Silage was available ad-libitum for heifers offered 3 kg but was restricted to 1 kg DM/day for heifers on ad-libitum concentrate intake. Both concentrates contained 14% crude protein. After 100 d, heifers were treated with an intravaginal progesterone releasing device (CIDR) for 7 d, and superovulation was initiated 60 h before CIDR withdrawal. Heifers received pFSH (a total of 265 mg NIH-FSH-P1 equivalent) administered over 8 injections at 12 h intervals with the last 2 injections administered at 12 and 24 h after CIDR withdrawal; they were inseminated at 56 and 72 h after CIDR withdrawal without reference to estrus. Heifers were slaughtered 6, 7 or 8 d after the first insemination, and embryos were flushed from the uterus with PBS and were graded morphologically. Statistical analyses were performed using analysis of variance. There was no interaction between level and type of diet, and thus data for the main effects are presented separately. Final live weights at the end of the experiment and carcass weights for heifers offered ad-libitum concentrate (643.8+/-6.9 kg; 354+/-8 kg, respectively) were higher (P<0.01) than those of heifers offered 3 kg concentrate (613.1+/-7.5 kg; 338.4+/-3.2 kg, respectively) while live weights and carcass weights of heifers offered barley (625.6+/-8.1 and 345.4+/-4.1 kg, respectively) or citrus/beet pulp concentrate (631.4+/-7.0 and 348.0+/-3.1 kg, respectively) were not different (P>0.05). Superovulatory responses (number of corpora lutea at slaughter) was greater (P<0.06) when heifers were offered 3 kg (15.5+/-1.6) than when offered ad-libitum concentrates (12.3+/-1.4). However, the superovulatory response for both citrus/beet pulp (14.4+/-1.5) and barley (13.4+/-1.5) diets were not different (P>0.05). Heifers offered 3 kg concentrates produced greater (P<0.05) numbers of transferable embryos (4.8+/-0.7) compared with heifers fed ad-libitum concentrates (2.8+/-0.4). Heifers offered citrus/beet pulp produced greater (P<0.05) numbers of transferable embryos (4.8+/-0.7) than heifers offered barley (2.9+/-0.5). These data indicate that high concentrate intake has a negative effect on embryo yield and quality and that a barley compared with citrus/beet pulp based concentrate has a negative effect on embryo quality following superovulation in beef heifers.     

Toxic effects of mercury(II), cadmium(II) and lead(II) porphyrins on Trypanosoma brucei brucei growth

The effects of free mercury(II), cadmium(II) and lead(II) ions and their metalloporphyrin-derivatives on Trypanosoma brucei brucei growth in culture were studied. All experiments were conducted in the dark. IC(50) values on growth obtained in 24-h time-course experiments were 1.5 x 10(-7), 2.4 x 10(-6), 4.4 x 10(-6) and 2.6 x 10(-5) M for mercury(II) porphyrin, cadmium(II) porphyrin, lead(II) porphyrin and free base porphyrin, respectively. While the IC50 values for Hg2+, Cd2+ and Pb2+ were 3.6 x 10(-6), 1.5 x 10(-5) and 1.6 x 10(-5) M, respectively. These results clearly indicate that the toxicity of the metalloporphyrin complexes of mercury(II), cadmium(II) and lead(II) to T. b. brucei parasites was much higher compared to their free metal ions and free base porphyrin at low concentrations. It was also observed after 8 h incubation that the metalloporphyrins were effective in inhibiting the division of the parasites at concentrations >1.25 x 10(-7) M for mercury(II) porphyrin, concentrations >1.2 x 10(-6) M for cadmium(II) and lead(II) porphyrins and at concentrations >3.6 x 10(-6) M for Hg2+ ion. These observations were not detected in samples treated with the free metal ions and the free base porphyrin at the same concentrations. Interestingly, trypanosomes treated with metalloporphyrin complexes displayed different morphological features from those cells treated with free base porphyrin or metal ions. The chemotherapeutic potential of the metalloporphyrins of H2TMPyP for treatment of African trypanosomiasis is discussed.     

A comparison of chloride, bromide, and sucrose dilution volumes in neonatal pigs

Use of 36Cl, 82Br, and [3H]sucrose to estimate extracellular water volume was evaluated in 14 piglets (7-14 days old). 36Cl and 82Br were distributed in approximately the same volume, but a period of 5-6 hr after injection was required to reach equilibrium in the neonatal pig. Dilution volumes calculated before equilibration (2-5 hr) for 36Cl (326 +/- 11 ml/kg) and 82Br (328 +/- 13 ml/kg) were different from equilibration (6-8 hr) phase volumes (356 +/- 13 ml/kg and 355 +/- 13 ml/kg, respectively; P less than 0.001). A 3-hr sample estimated the same volume distribution calculated by extrapolation of the 6- to 8-hr period because of the relationship between the two slopes of the plasma clearance curves. After the 82Br and 36Cl had achieved equilibration, each was distributed in a volume equivalent to total body chloride space (362 +/- 29 ml/kg) measured by neutron activation; no statistical differences were found (P = 0.6). The early equilibration phase measured a 10% smaller, faster exchangeable fraction of total body Cl. Sucrose dilution volume (332 +/- 19 ml/kg) required multiple plasma samples for extrapolation and measured a dilution volume 7% smaller (P less than 0.05) than total body chloride space.     

Development of new insulinomimetic zinc(II) picolinate complexes with a Zn(N2O2) coordination mode: structure characterization, in vitro, and in vivo studies

Three zinc(II) complexes of picolinic acid and its derivatives with a Zn(N2O2) coordination mode were prepared and evaluated for their insulinomimetic activities by in vitro and in vivo studies. By introducing an electron-donating methyl group into the picolinate ligand (pic), bis(6- or 3-methylpicolinato)zinc(II) complexes [Zn(6-mpa)2 or Zn(3-mpa)2, respectively] were prepared. The Zn(6-mpa)(2) complex was crystallized as a water adduct [Zn(6-mpa)2(H2O)].H2O, in which two carboxylate oxygens and two pyridine nitrogens of 6-mpa and a water oxygen coordinate to a zinc(II) with a trigonal bipyramidal geometry. By in vitro evaluation of the inhibition of free fatty acid (FFA) release from isolated rat adipocytes in the presence of epinephrine, the insulinomimetic activities of Zn(pic)2, Zn(6-mpa)2, and Zn(3-mpa)2 (IC50=0.64 +/- 0.13, 0.31 +/- 0.05, and 0.40 +/- 0.07 mM, respectively) were found to be higher than those of VOSO(4) (IC50=1.00 mM) and ZnSO(4) (IC50=1.58 +/- 0.05 mM) in terms of IC50 value, the 50% inhibition concentrations for the FFA release from the adipocytes. Then, Zn(6-mpa)2, which exhibited the highest in vitro insulinomimetic activity among three complexes examined, was given at a dose of 3.0 mg (45.9 micromol) Zn/kg body weight to KK-A(y) mice with type 2 diabetes mellitus by daily intraperitoneal injections for 14 days and it was found that the hereditary high blood glucose levels were lowered during the administration of the complex. The improvement of diabetes mellitus was confirmed with the oral glucose tolerance test.     

Boronated dipeptide borotrimethylglycylphenylalanine as a potential boron carrier in boron neutron capture therapy for malignant brain tumors.

Takagaki, M., Ono, K., Masunaga, S-I., Kinashi, Y., Oda, Y., Miyatake, S-I., Hashimoto, N., Powell, W., Sood, A. and Spielvogel, B. F. Boronated Dipeptide Borotrimethylglycylphenylalanine as a Potential Boron Carrier in Boron Neutron Capture Therapy for Malignant Brain Tumors. Radiat. Res. 156, 118-122 (2001).A boronated dipeptide, borotrimethylglycylphenylalanine (BGPA), was synthesized as a possible boron carrier for boron neutron capture therapy (BNCT) for malignant brain tumors. In vitro, at equal concentrations of (10)B in the extracellular medium, BGPA had the same effect in BNCT as p-boronophenylalanine (BPA). Boron analysis was carried out using prompt gamma-ray spectrometry and track-etch autoradiography. The tumor:blood and tumor:normal brain (10)B concentration ratios were 8.9 +/- 2.1 and 3.0 +/- 1.2, respectively, in rats bearing intracranial C6 gliosarcomas using alpha-particle track autoradiography. The IC(50), i.e. the dose capable of inhibiting the growth of C6 gliosarcoma cells by 50% after 3 days of incubation, was 5.9 x 10(-3) M BGPA, which is similar to that of 6.4 x 10(-3) M for BPA. The amide bond of BGPA is free from enzymatic attack, since it is protected from hydrolysis by the presence of a boron atom at the alpha-carbon position of glycine. These results suggest promise for the use of this agent for BNCT of malignant brain tumors. Further preclinical studies of BGPA are warranted, since BGPA has advantages over both BPA and BSH.     

Opioid action on luteinizing hormone secretion in newborn pigs: paradoxical effect of naloxone

German Landrace piglets, 6-7 days of age, received either saline (9 males, 8 females), 0.5 mg naloxone/kg body weight (7 males, 7 females), 2.0 mg naloxone/kg (7 males, 8 females) or 0.5 mg DADLE (potent leu-enkephalin analog)/kg (7 males, 7 females) through a catheter inserted into the jugular vein 2-4 days previously. Male or female piglets were allocated randomly, within litter, to the different experimental groups. Blood samples were withdrawn for a period of 240 min at 10-min intervals for the first 60 min following injection and at 20-min intervals for the rest of the test period. Piglets were separated from their mother via a detachable wall and were allowed to suckle every 50 min. DADLE failed to alter plasma levels of LH in both males and females. Naloxone induced a significant (P less than 0.01) decrease in LH concentrations in females 10 to 60 min after injection (saline: 2.3 +/- 0.2 ng/ml plasma (SEM); 0.5 mg naloxone/kg: 1.0 +/- 0.2 ng/ml plasma and 2 mg naloxone/kg 1.2 +/- 0.4 ng/ml plasma). In males low doses of naloxone reduced plasma LH levels 10 to 40 min after injection (saline: 2.0 +/- 0.3 ng/ml plasma and 0.5 ng naloxone/kg: 1.1 +/- 0.3 ng/ml), whereas a decrease in plasma LH levels occurred 80 to 140 min after injection of high doses of naloxone (saline: 2.1 +/- 0.2 ng/ml and 2 mg naloxone/kg: 1.0 +/- 0.2 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandins and control of breathing in newborn piglets

To investigate the possible role of prostaglandins in regulation of postnatal breathing, phrenic neural activity (PMO) was recorded as an index of breathing in 42 anesthetized, paralyzed piglets less than 30 days of age (weight 2.4 +/- 0.2 kg, age 9.9 +/- 1.5 days) who were mechanically ventilated with 100% O2 at a fixed tidal volume (8-10 ml/kg). End-tidal CO2 was held constant by an electronic servocontroller which adjusted ventilator rate; ventilator rate was monitored as an index of CO2 production. Rectal temperature was maintained at 39.0 +/- 0.2 degrees C. The effects on PMO of intravenous and brain ventricular injections of NaCl and agents active in the prostaglandin cascade were compared. Intravenous (0.25-1.0 mg/kg, n = 9) and brain (5-33 micrograms/kg, n = 6) indomethacin, a cyclooxygenase inhibitor, doubled PMO within 30 min. Intravenous (1-10 micrograms/kg, n = 6) and brain (1-40 micrograms/kg, n = 6) prostaglandin E1 inhibited PMO by one-half at 10 and 30 min.     

Circulating gonadotrophins and follicular dynamics in anestrous ewes after treatment with estradiol-17beta.

Plasma FSH, LH, estradiol (E2) and progesterone (P4) profiles and patterns of follicular growth and regression by ultrasonography were determined after E2 treatment (1 microg/kg) in anestrous ewes. Fifteen ewes were treated with one (group I, n=7) or two (group II, n=4) i.m. injections of E2 with a 24h interval, or two oil injections with a 24h interval (group C, n=4). Blood samples for E2, P4, FSH and LH determinations were collected daily 4 days before the initiation of the treatment (day 0), when bleeding increased to every 2h starting 2h before treatment until 56h after the first injection and from then on every 6h until day 8, and twice per day till the end of the experiment (day 9). During the experimental period (days -4 to 9), transrectal ultrasonic examinations were carried out daily using a 7.5 MHz linear array probe. Number and size of follicles > or =3mm in diameter were recorded. No estrous was detected before, during or after treatment. LH and FSH surges were observed 10-18h after the first E2 injection. The second E2 injection stimulated another release of LH but no surges. E2 inhibited FSH levels before the surge and the second E2 injection induced a longer inhibition. No ovulation was detected by ultrasonography during the experimental period and P4 levels remained low (<0.7 nmol/l) before, during and after the treatment in all ewes. There was an effect of E2 treatment on the diameter of the largest follicle, a decrease could be observed 3 days after the first injection in both ewes of groups I and II. The E2-treated groups had a higher frequency of ewes showing wave emergence on day 3 (day 1.5+/-1,2.4+/-0.4 and 2.5+/-0.5 for control, groups I and II). LH and FSH surges were observed after E2 treatment, but were not able to provoke ovulation neither luteinization. In contrast, the treatment was associated with the regression of the largest follicle and with emergence of a new follicular wave on day 3.     

Hypertonic saline dextran after burn injury decreases inflammatory cytokine responses to subsequent pneumonia-related sepsis

The present study examined the hypothesis that hypertonic saline dextran (HSD), given after an initial insult, attenuates exaggerated inflammation that occurs with a second insult. Adult rats (n = 15 per group) were divided into groups 1 (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) + 4 ml.kg(-1).% burn(-1) lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR), and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns; groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus pneumoniae (4 x 10(6) colony-forming units) 7 days after burn. Groups 4-8 were studied 8 days after burn and 24 h after IT septic challenge. When compared with sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD-treated burns. Cardiac inflammatory responses (pg/ml TNF-alpha) were evident with IS (170 +/- 10) but not HSD (45 +/- 5) treatment vs. sham treatment (80 +/- 15). Pneumonia-related sepsis 8 days after IS-treated burns (group 7) exacerbated TNF-alpha responses/contractile dysfunction vs. IS-treated burns in the absence of sepsis (P < 0.05). Sepsis that occurred after HSD-treated burns (group 8) had less myocyte TNF-alpha secretion/better contractile function than IS-treated burns given septic challenge (group 7, P < 0.05). We conclude that an initial burn injury exacerbates myocardial inflammation/dysfunction occurring with a second insult; giving HSD after the initial insult attenuates myocardial inflammation/dysfunction associated with a second hit, suggesting that HSD reduces postinjury risk for infectious complications.     

The length of the cycle of seminiferous epithelium in goats (Capra hircus).

This is the first report in literature showing the length of the seminiferous epithelium cycle in goats. In the present study, the duration of spermatogenesis was estimated using intratesticular injections of tritiated thymidine. Animals were castrated at 4 h, 7 days, and 11 days after injections. The duration of each spermatogenic cycle in goats is 10.6 +/- 0.5 days (SEM). Considering that the total duration of spermatogenesis takes about 4.5 cycles of seminiferous epithelium, spermatogenesis was estimated to last 47.7 days. The approximate primary spermatocytes life span is 14.1 days, while spermiogenesis in goats lasts 14.9 days. Staging in goats was based on the tubular morphology, where 8 stages of the cycle are yielded for all species. The relative stage frequencies in goats, based on 400 seminiferous tubule cross sections for each animal were as follows: stage 1: 15.8 +/- 1.0%; stage 2: 12.8 +/- 0.5%; stage 3: 20.5 +/- 0.9%; stage 4: 10.7 +/- 0.7%; stage 5: 11.6 +/- 0.6%; stage 6: 9.3 +/- 1.1%; stage 7: 7.6 +/- 0.4%; stage 8: 11.7 +/- 0.6%. The pre-meiotic, meiotic and post-meiotic phases' relative frequencies were 49.1%, 10.7% and 40.2%, respectively. The duration of spermatogenesis in goats is very similar to that found in rams.     

叶面喷施微肥对川白芷主要有效成分含量的影响

在川白芷生长旺盛期叶面喷施锌、硼、钼,研究微量元素锌、硼、钼配合喷施对川白芷主要有效成分含量的影响以及最适宜的喷施量.结果表明: 叶面喷施锌、硼、钼有利于川白芷欧前胡素和总香豆素含量的提高,对异欧前胡素含量的影响不显著;硼对欧前胡素和总香豆素含量的积累影响最大,锌次之,钼最小;硼和钼互作对欧前胡素含量有拮抗效应,锌和硼互作对总香豆素含量有协同效应;施锌0.15～0.24 kg·hm^-2、硼2.02～2.36 kg·hm^-2、钼0.08～0.13 kg·hm^-2时,川白芷总香豆素含量≥0.7%;施锌0.15～0.20 kg·hm^-2、硼1.37～1.47 kg·hm^-2、钼0.09～0.13 kg·hm^-2时,欧前胡素含量≥0.2%.叶面喷施锌、硼、钼有利于川白芷中香豆素类成分的积累和品质的提高.     

Secretory patterns of LH and FSH during development and hypothalamic and hypophysial characteristics following development of steroid-induced ovarian follicular cysts in dairy cattle

Two experiments were conducted to (1) investigate developmental endocrinology of ovarian follicular cysts (cysts) in cattle and (2) evaluate effects of cysts on hypothalamic and hypophysial characteristics. Cysts were induced with oestradiol-17 beta (15 mg) and progesterone (37.5 mg) dissolved in alcohol and injected s.c. twice daily for 7 days. Cysts were defined as the presence of follicular structures (which may or may not have been the same structure) of 2.0 cm in diameter or greater that were present for 10 days without ovulation and corpus luteum development. In Exp. 1,22 non-lactating, non-pregnant Holstein cows were allocated to 3 groups. Beginning on Day 5 (oestrus = Day 0) of the oestrous cycle, 7 cows (Controls) were treated with twice daily s.c. injections of ethanol (2 ml/injection) for 7 days. Luteolysis was then induced with PGF-2 alpha and blood samples were collected daily every 15 min for 6 h from the morning after the PGF-2 alpha injection (Day 13) until oestrus. Steroids to induce cysts were injected as previously described into the remaining cows (N = 15). Three blood samples were collected at 15-min intervals every 12 h throughout the experimental period. Additional blood samples were collected every 15 min for 6 h on a twice weekly basis. After steroid injections, follicular and luteal structures on ovaries were not detected via rectal palpation for a period of 36 +/- 4 days (static phase). Then follicles developed which ovulated within 3-7 days (non-cystic; N = 7) or increased in size with follicular structures present for 10 days (cystic; N = 8). Mean (+/- s.e.m.) concentrations of LH, FSH, oestradiol-17 beta and progesterone in serum remained low and were not different during the static phase between cows that subsequently developed cysts or ovulated. During the follicular phase, mean serum concentration of LH (ng/ml) was higher (P less than 0.1) in cows with cysts (2.9 +/- 0.2) than in cows without cysts (1.1 +/- 0.1) or control cows (1.4 +/- 0.2). In addition, LH pulse frequency (pulses/6 h) and amplitude (ng/ml) were higher (P less than 0.1) in cows with cysts (3.6 +/- 0.3 and 2.2 +/- 0.3, respectively) than in non-cystic (2.3 +/- 0.2 and 1.0 +/- 0.2, respectively) and control (1.8 +/- 0.1 and 1.1 +/- 0.2, respectively) groups during the follicular phase. There were no differences in the FSH, oestradiol-17 beta or progesterone characteristics in cows of any of the 3 groups during the follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bradykinin in reflex cardiovascular responses to static muscular contraction

We examined the contribution of bradykinin to the reflex hemodynamic response evoked by static contraction of the hindlimb of anesthetized cats. During electrical stimulation of ventral roots L7 and S1, we compared the cardiovascular responses to hindlimb contraction before and after the following interventions: inhibition of converting enzyme (kininase II) with captopril (3-4 mg/kg, n = 6); inhibition of kallikrein activity with aprotinin (Trasylol, 20,000-30,000 KIU/kg, n = 8); and injection of carboxypeptidase B (500-750 U/kg, n = 7). Treatment with captopril augmented the rise in mean arterial blood pressure and maximal time derivative of pressure (dP/dt) caused by static contraction from 21 +/- 3 to 39 +/- 7 mmHg and 1,405 +/- 362 to 2,285 +/- 564 mmHg/s, respectively. Aprotinin attenuated the contraction-induced rise in mean arterial blood pressure (28 +/- 4 to 9 +/- 2 mmHg) and maximal dP/dt (1,284 +/- 261 to 469 +/- 158 mmHg/s). Carboxypeptidase B reduced the cardiovascular response to static contraction. Thus the mean arterial blood pressure response was decreased from 36 +/- 12 to 24 +/- 11 mmHg, maximal dP/dt from 1,618 +/- 652 to 957 +/- 392 mmHg/s, and heart rate from 12 +/- 2 to 7 +/- 1 beats/min. These data suggest that stimulation of muscle afferents by bradykinin contributes to a portion of the reflex cardiovascular response to static contraction.     

Effect of dose schedule of vitamin E and hydroxethylruticide on intestinal toxicity induced by adriamycin

CDF1 mice receiving Adriamycin, 12 mg/kg IP develop a toxic GI mucositis. The mean survival in CDF1 mice after Adriamycin injection was found to be 6.5 +/- 2.0 weeks and could be increased by alcohol or acetate Vitamin E pretreatment (with 2 g/kg qDx7d) to 22.06 +/- 12.3 weeks or by treatment with Venoruton after Adriamycin (qDx7 with 1.5 g/kg) to 23.7 +/- 12.7 weeks. Other schedules were ineffective or harmful. The ability of Venoruton to enhance survival when given after Adriamycin encouraged us to proceed to tumor bearing mice. The maximum survival with CDF1 mice bearing 5 X 10(6) L1210 cells was 1 +/- 0.2 week which could be increased to 2.17 +/- 0.8 weeks with optimal dose Adriamycin (10 mg/kg). Optimum survival with Venoruton and a single dose of Adriamycin was 2.45 +/- 0.91 weeks with Venoruton, 1.5 g, qd X 14, and 12 mg/kg Adriamycin. Treatment of L1210 bearing mice with Adriamycin, 10 mg/kg on days 1 and 8, yielded a survival of 2.23 +/- 0.7 weeks. An equitoxic regimen of Adriamycin, 11 mg/kg on days 1 and 9, plus Venoruton, 1.5 g, qd X 14, increased survival 30% to 3.08 +/- 2.9 weeks. Venoruton is a promising agent to increase the therapeutic index of Adriamycin.