No evidence for a direct vasodilatory effect of celiprolol on human vasculature in vivo or in vitro

Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arterial celiprolol (1-100 micrograms/min i.a.) on forearm blood flow (FBF). Forearm blood was measured by venous occlusion plethysmography. Possible vasorelaxant actions of celiprolol on human vascular smooth muscle were studied using segments of isolated human saphenous vein in vitro. The effect of celiprolol was investigated on resting tone or noradrenaline induced tone. Possible alpha 2-adrenoceptor antagonist effects of celiprolol were assessed using celiprolol as an antagonist of BHT933 induced constriction. Celiprolol was without significant effect on FBF and failed to relax isolated saphenous vein segments preconstricted with noradrenaline. The weak alpha 2-adrenoceptor antagonist action of celiprolol was demonstrable in human saphenous vein. This study does not provide evidence for a direct vasodilatory effect of celiprolol on human vasculature.     

Uterine artery resistance and anxiety in the second trimester of pregnancy.

OBJECTIVE: To investigate the association between maternal anxiety and uterine artery resistance index (RI) at 20 weeks of gestation. METHODS: Uterine artery blood flow was assessed using color Doppler ultrasound and maternal anxiety was measured using the Hospital Anxiety and Depression (HAD) scale in 96 healthy primigravid women attending consecutively for their routine 20-week anomaly scan. RESULTS: The mean uterine artery RI was 0.54 (95% confidence interval, 0.52-0.56) and the median HAD anxiety score was 6 (range, 0-20). There was no association between RI and anxiety scores (r = 0.09, P = 0.36). Women scoring as definite cases of anxiety did not have a significantly elevated uterine artery RI or increased frequency of waveform notching compared to women with doubtful or no anxiety. CONCLUSIONS: The data of this study do not suggest a significant association between maternal anxiety and uterine artery RI at 20 weeks of gestation in healthy primigravid women with normally developing pregnancies. A prospective cohort study would be useful to determine the nature of the relationship between maternal anxiety, alteration in uterine artery blood flow and abnormal pregnancy outcome.     

The effect of monoclonal antibodies to calcitonin gene-related peptide (CGRP) on CGRP-induced vasodilatation in pig coronary artery rings.

1. The modification of the vasodilator effect of calcitonin gene-related peptide (CGRP) by a panel of monoclonal antibodies (MAbs), which map to discrete epitopes on the CGRP molecule, was investigated in pig coronary artery rings (PCA). The preparations were pre-constricted with acetylcholine (3 x 10(-7) M) and concentration-response curves to CGRP (2 x 10(-10)-2.56 x 10(-8) M) were obtained in the presence or absence of each MAb. 2. CGRP caused a concentration-dependent relaxation of PCAs which reached a maximum (98.2 +/- 4.8%, n = 25) at 1.28 x 10(-8) M and gave an EC50 of 3.8 +/- 0.8 x 10(-9) M. 3. Two MAbs which map to the N-terminal, CN1 and CRA3, did not affect the CGRP response whilst a third, CRA5, significantly inhibited its effect. 4. The C-terminal MAb, CRA2, did not modify the CGRP response whilst, in contrast, CB3 (C-terminal) potentiated its effect. A similar augmentation of the CGRP-induced vasodilatation was seen in the presence of the middle-region MAb, CRA8. 5. These results suggest that regional specific MAbs can modify the vasodilator effect of CGRP causing either inhibition (CRA5, N-terminal) or potentiation (CB3, C-terminal; CRA8, middle region).     

Intracapsular tonsillar reduction (partial tonsillectomy): reviving a historical procedure for obstructive sleep disordered breathing in children.

OBJECTIVE: We sought to reintroduce a historical procedure-intracapsular tonsillar reduction (partial tonsillectomy or tonsillotomy)-for tonsillar hypertrophy causing obstructive sleep disordered breathing (OSDB) in children, as well as to determine whether partial tonsillectomy, compared with conventional (total) tonsillectomy when performed by more than one surgeon, is equally effective for the relief of OSDB while resulting in less pain and more rapid recovery. STUDY DESIGN: We conducted a retrospective case series at a tertiary children's hospital. The charts of children who underwent partial tonsillectomy and total tonsillectomy (1998 through 2002) for postoperative complications were reviewed. The caregivers were surveyed to assess postoperative pain, rapidity of recovery, and effectiveness of surgery for relieving symptoms of OSDB. RESULTS: Two hundred forty-three children underwent partial tonsillectomy and 107 children underwent total tonsillectomy. There were no significant differences in immediate and delayed complications between the groups. Both operations were equally effective in relieving OSDB. Children who had partial tonsillectomy had significantly less postoperative pain and significantly more rapid recovery. CONCLUSION: Intracapsular tonsillar reduction with an endoscopic microdebrider relieves OSDB as effectively as conventional tonsillectomy, but results in less postoperative pain and a more rapid recovery.     

Seasonal effects on seminal quality, plasma hormone concentrations, and GnRH-induced LH response in fertile and subfertile stallions.

Seasonal effects on hormonal and seminal parameters in subfertile stallions have not been well documented and could provide information that is needed to understand the underlying endocrine mechanisms associated with testicular dysfunction. Such information may be useful in developing diagnostic tools to identify those stallions who are candidates for treatment. This investigation characterizes and compares the effects of season on endocrine function and seminal quality in fertile and subfertile stallions. Eight fertile and six subfertile stallions between the ages of 5 and 18 years were injected intravenously once every hour for 3 hours with either 1 mL saline on the first experimental day or 5 micrograms gonadotropin-releasing hormone in 1 mL saline on the second experimental day during the nonbreeding and breeding season. Heparinized blood samples were collected periodically through a jugular catheter before and after treatment for analysis of luteinizing hormone, follicle-stimulating hormone, testosterone, and estrogen conjugates by radioimmunoassay. Semen samples were collected twice, 1 hour apart, from all stallions in both seasons for analysis of volume, concentration, motility, pH, and morphology. A series of low intravenous doses (5 micrograms) of gonadotropin-releasing hormone induced a significant luteinizing hormone response (P less than 0.05) compared with saline treatment in both fertile and subfertile stallions. Fertile stallions had a twofold higher (P less than 0.05) net increase in plasma luteinizing hormone levels (peak levels minus baseline levels) in the breeding seasons than in the nonbreeding season. The magnitude of the luteinizing hormone response relative to baseline levels in fertile stallions, however, was one-and-one-half times greater (P less than 0.05) in the nonbreeding season than in the breeding season. In contrast, season did not have an effect on the net increase in plasma luteinizing hormone or the magnitude of the luteinizing hormone response relative to baseline levels in subfertile stallions. The net increase in plasma luteinizing hormone was similar between the two groups of stallions in both seasons. The magnitude of luteinizing hormone response relative to baseline levels, however, was lower (P less than 0.05) in subfertile stallions (141 +/- 14%) than in fertile stallions (235 +/- 46%) in the nonbreeding season; the two groups exhibited similar responses in the breeding season. Compared with fertile stallions, subfertile stallions had twofold to fourfold higher (P less than 0.05) plasma levels of gonadotropins and similar testosterone levels. The number of total progressively motile sperm was lower (P less than 0.05) in subfertile stallions in both seasons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.     

A system for tissue-specific gene targeting: transgenic mice susceptible to subgroup A avian leukosis virus-based retroviral vectors.

Avian leukosis viruses (ALVs) have been used extensively as genetic vectors in avian systems, but their utility in mammals or mammalian cell lines is compromised by inefficient viral entry. We have overcome this limitation by generating transgenic mice that express the receptor for the subgroup A ALV under the control of the chicken alpha sk-actin promoter. The skeletal muscles of these transgenic animals are susceptible to efficient infection by subgroup A ALV. Because infection is restricted to cell lineages that express the transgene, the method has utility for studies of development and oncogenesis and will provide models for tissue-specific gene therapy.