The distribution of (-)-propranolol in the isolated rabbit iris

It has been postulated that propranolol lowers the intraocular pressure by adrenergic neurone block. However, in the isolated iris of albino rabbits, there was only a small degree of cocaine-sensitive (i.e., neuronal) accumulation of ³H-(-)-propranolol, and none at all after pretreatment of the animals with reserpine. Moreover, after preloading of the iris with ³H-(-)-propranolol, veratridine failed to release any labelled material. Hence, any adrenergic neurone blocking action of propranolol is highly unlikely.Albino and pigmented irides were first exposed to ³H-(-)-propranolol and then washed out. The results and their compartmental analysis indicated an extensive binding of ³H-(-)-propranolol in or at pigment cells; the binding is characterized by a low dissociation constant. It is very likely that the initial binding and the subsequent slow dissociation from pigment cells explains the long duration of action of beta-adrenoceptor antagonists in human therapy.     

Congenital lens coloboma and associated pathologies

Coloboma of the lens is characterized by notching of the equator of the lens. The cause of the condition is faulty development of the zonule. The lens deprived of its normal pull in the defective region is thicker and more spherical as if there were no loss of its substance. We report five cases of lens coloboma and localized zonular defect without any associated systemic anomalies. One case included retinal detachment; another included an iris coloboma; and a third included iris, choroid and optic disk colobomas and retinal detachment with lens coloboma. The remaining two cases were without associated ocular anomalies. The pathogenic mechanisms and relationship of this defect with the differentiation of the tertiary vitreous and development of the zonule is discussed. The defect most likely occurs in the third to fourth months of gestation during differentiation of the tertiary vitreous in response to toxic, inflammatory or genetic factors.     

Effects of capsaicin,tachykinins, calcitonin gene-related peptide and bradykinin in the pig iris sphincter muscle

Summary Capsaicin-sensitive sensory neurons of the rabbit iris, by releasing tachykinins, exert a major role in the control of pupil motility in response to various noxious stimuli. However, the contribution of sensory innervation to the regulation of iris smooth muscle tone in other mammals species is not known. We have studied the effects produced by electrical field stimulation, capsaicin, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and bradykinin in the isolated iris sphincter muscle of the pig.Capsaicin (10 M): a) contracted the isolated sphincter muscle and; b) released immunoreactivity for substance P (SP-LI) and CGRP (CGRP-LI) from this preparation. These two effects were no longer observed at the second exposure to the drug. Electrical field stimulation (10 Hz, 60 V, 0.5 ms for 5 s) produced a biphasic contractile response. The rapid component was inhibited by atropine (1 M), while the delayed response was blocked by previous exposure to capsaicin (10 M).Substance P and neurokinin A consistently produced contraction of the pig iris sphincter muscle, substance P being more potent than neurokinin A. CGRP induced a contractile response in more than 50% of the preparations. The tachykinin antagonist [D-Argl, D-Trp^7,9, Leu¹¹-substance P (3 M) blocked: a) the effect of substance P (1 nM); b) the delayed response to electrical field stimulation and; c) reduced by more than 50% response to capsaicin. Bradykinin (10 M) failed to release either SP-LI or CGRP-LI. The contractile response evoked by bradykinin was unaffected by in vitro pretreatment with capsaicin (10 M).The existence in the pig iris of capsaicin-sensitive sensory fibres releasing neuropeptides and thus regulating sphincter muscle tone is proposed. Send offprint requests to Dr. P. Geppetti at the above address     

Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris

Summary The potencies of several muscarine receptor antagonists in blocking either the autoinhibition of acetylcholine release or the muscarinic contraction of the sphincter muscle upon acetylcholine release were investigated in the guinea-pig iris. The agonist at pre- or postjunctional muscarine receptors was acetylcholine released upon field stimulation (5.5 Hz, 2 min) of the irides preloaded with ¹⁴C-choline. The stimulation-evoked ¹⁴C-overflow was doubled in the presence of atropine 0.1 mol/l but unaffected by the agonist (±)-methacholine (50 mol/l). Thus, under the present stimulation conditions, the autoinhibition of acetylcholine release on the guinea-pig iris cholinergic nerves was nearly maximally activated. Isotonic contractions of the irides upon field stimulation consisted of a rapid, atropine (0.1 mol/l). peak phase followed by a sustained contraction which involved a cholinergic and a non-cholinergic stimulation of the sphincter muscle. The M₂-selective antagonists methoctramine (10 mol/l) and gallamine (100 µmol/l). increased both the ¹⁴Goverflow and the peak contractions evoked by field stimulation. In contrast, the M₃-selective antagonist hexahydrosiladifenidol (0.1–10 mol/l) failed to affect the evoked ¹⁴C-release but concentration-dependently (1–10 mol/l) reduced the iris contractions. Pirenzepine (10 mol/l) enhanced the evoked ¹⁴C-overflow and inhibited the peak contractions (0.1–10 mol/l; maximal effect at 10 mol/l). The low potency of the antagonist at both receptor sites indicates that an M₁ muscarine receptor is not involved. The results are consistent with the idea of M₂ muscarine receptors mediating autoinhibition of acetylcholine release in the guinea-pig iris and M₃-like receptors inducing the contraction of the sphincter muscle. Send offprint requests to I. T. Bognar at the above address     

莪术注射液抑制K562细胞增殖及诱导其凋亡的研究

目的：探寻新的抗白血病药物。方法：采用ＭＴＴ法,以柔红霉素（ＤＮＲ）、阿糖胞苷（Ａｒａ－Ｃ）和羟基脲作对照,了解莪术注射液对Ｋ５６２细胞增殖抑制作用;通过流式细胞仪检测和ＤＮＡ凝胶电泳,观察莪术注射液诱导Ｋ５６２细胞凋亡的情况。结果：莪术注射液对Ｋ５６２细胞不仅具有强大的增殖抑制作用,功效明显强于对照ＤＮＲ、Ａｒａ－Ｃ和羟基脲;而它更主要的作用是诱导Ｋ５６２细胞不仅具有强大的增殖抑制作用,功效明显     

虎杖蒽醌化合物抗CVB3病毒的实验研究

目的：为了解虎杖蒽醌化合物晶Ⅰ,晶Ⅳ抗ＣＶＢ３病毒的药效从而明确虎杖的抗病毒性能并开发利用。方法;以病毒唑为阳性对照,利用空斑减数实验进行研究。结果：在ＨＥＰ－２细胞系统中,晶Ⅰ对ＣＶＢ３直接杀灭,增殖抑制,感染阻断ＥＤ５０分别为１．５４μｇ／ｍＬ,８．３４μｇ／ｍＬ,３．０６μｇ／ｍＬ,晶Ⅳ的相 系数分别为１．７９μｇ／ｍＬ,７．０５μｇ／ｍＬ,３．１７μｇ／ｍＬ,而病毒唑的相应系数分别为６．２     

Aniridie et tumeur de Wilms : deux cas de néphroblastome fœtal rhabdomyomateux

Background.

Wilms tumor is associated in 7 to 10 % of patients with congenital abnormalities. Among those, aniridia is the most constant feature of the WAGR syndrome that includes, in one third of cases, Wilms tumor. We report two cases of aniridia associated with fetal rhabdomyomatous nephroblastoma.

Case reports.

Case 1. A one-year old girl with congenital aniridia was admitted for macroscopic hematuria. Abnormal ultrasonography and tomodensitometry revealed a large, bilateral, kidney tumor. The patient was given actinomycin and vincristine, without efficacy. Bilateral tumorectomy was performed 6 months later and the histological study showed a fetal rhabdomyomatous nephroblastoma. This patient is in remission at the age of 5. Case 2. A boy, also with congenital aniridia, presented with macroscopic hematuria at the age of 2 years revealing a nephroblastoma located on his right kidney. Preoperative chemotherapy remained uneffective and the nephrectomy performed 1 month later permitted the diagnosis of fetal rhabdomyomatous nephrolastoma. The patient is well 4 years later.

Conclusion.

Both cases of fetal rhabdomyomatous nephroblastoma, a histological variant of Wilms tumor, seem to be the first reported in the WAGR syndrome.     

Methyldopa produces central inhibition of parasympathetic activity in the cat

Summary -Methyldopa (10–100 mg/kg i.v.) produced a dose-dependent pupillary dilation in anaesthetized cats which was antagonized by subsequent administration of yohimbine hydrochloride (0.5 mg/kg i.v.). The peak effects were observed approximately 2–3h after injection. This -methyldopa-induced mydriasis was present only when the parasympathetic innervation to the iris was intact. Prior treatment with yohimbine (0.5 mg/kg i.v.) 30 min before -methyldopa also antagonized the mydriatic effect, whereas pretreatment with phenoxybenzamine (2.5 mg/kg i.v.) did not. In contrast, phenoxybenzamine, but not yohimbine, effectively antagonized the pupillary dilation produced by adrenaline (0.3–10.0 g/kg i.v.). These results suggest that -methyldopa produces mydriasis in the cat by means of CNS inhibition of tonic outflow from the oculomotor nucleus and that an -adrenergic inhibitory mechanism may be involved. This conclusion is supported further by experiments in which direct measurements of ciliary nerve activity were made.     

Purinoceptor-mediated modulation by endogenous and exogenous agonists of stimulation-evoked [3H]noradrenaline release on rat iris

Summary To investigate whether endogenous purinoceptor agonists affect the sympathetic neurotransmission in the rat isolated iris, and to classify the purinoceptors modulating exocytotic [³H]-noradrenaline release, we have determined the effect of adenosine receptor antagonists on, and the relative potency of selected agonists in modulating, the field stimulation-evoked (3 Hz, 2 min) [³H]-noradrenaline overflow. In addition, the apparent affinity constants of 8-phenyltheophylline (8-PT) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in antagonizing the prejunctional effects of purinoceptor agonists were estimated.The relatively A₁-selective DPCPX 10 and 100 nmol/l increased the evoked [³H]-noradrenaline overflow by about 25%–35%a indicating a minor inhibition of evoked release by endogenous purinoceptor agonists probably via an A₁ adenosine receptor. Whereas the A₁/A₂-antagonist 8-PT failed to increase the evoked [³H]-noradrenaline overflow in the absence of exogenous agonists (without or with dipyridamole 1 pmol/l present), the relatively A₂-selective antagonist CP-66,713 (4-amino-8-chloro -1-phenyl(1,2,4)triazolo(4,3-a)quinoxaline) 100 nmol/l decreased it by 20%–30% in the absence and continuous presence of DPCPX. This may be compatible with a minor A₂-mediated facilitation by an endogenous purinoceptor agonist.All exogenous agonists tested (except UTP 100 mol/l) inhibited the evoked [³H]-noradrenaline overflow. The relative order of agonist potency (IC4o, concentration in mol/l for inhibition of evoked release by 40%) was CPA (N⁶-(cyclopentyl)adenosine, 0.004) > R-PIA (R(–)N6-(2phenylisopropyl)adenosine, 0.066) = CHA (N⁶-(cyclohexyl)adenosine, 0.082) > NECA (N⁵-(ethyl-carboxamido)adenosine 0.44) > ADO (adenosine, 4.1). ATP was n early equipotent with ADO. Maximum inhibition was 70%–80% and similar for all agonists. Adenosine deaminase 1 u/ml failed to affect the ATP-induced, but abolished the adenosine-induced prejunctional inhibition. The adenosine uptake inhibitor S-p-nitrobenzyl-6-thioguanosine (NBTG) failed to enhance the potency of ADO and ATP. The A₁-selective antagonist DPCPX 10 nmol/l did not reduce the ATP potency indicating an effect of ATP per se not mediated via an A₁ purinoceptor.Prejunctional affinity constants of 8-PT were 6.07 when tested against adenosine (in the presence of dipyridamole), and 6.60 against CHA. The apparent -log K_B of DPCPX tested against CPA was 9.71. The high DPCPX affinity is compatible with an A₁ adenosine receptor mediating inhibition of sympathetic neurotransmission in rat iris. This receptor may not be the only prejunctional purinoceptor on rat iris sympathetic nerves. The receptor by which ATP acts prejunctionally in this tissue remains to be determined.This study was supported by the Deutsche Forschungsgemeinschaft (Fu 163/2 and 163/3) Send offprint requests to H. Fuder at the above address     

激光治疗闭角型青光眼

目的：评价激光虹膜切除治疗闭角型青光眼临床疗效。方法：应用Nd：YAG激光于上方或下方作周边虹膜切除。结果：107例122眼闭角型青光眼术后经过2—106月随访观察，成功115眼，失败7眼。结论：激光虹膜切除术治疗闭角型青光眼安全、有效。