Successful control of hidradenitis suppurativa with verapamil: a case report

An inappropriate immunologic response has been suggested to play a role in the pathogenesis of hidradenitis suppurativa (HS). Adalimumab was the first TNF‐α inhibitor approved for moderate to severe HS. We report on a case of HS (Hurley stage 2) in a 39‐year‐old man, who had received fusidic acid and isotretinoin treatments without evident benefit during the last 8 years. The patient noticed a reduction in the number of lesions and quality of life (DLQI from 27 to 6) in the 2 months following verapamil initiation for cluster headache. When verapamil was stopped, the lesions recurred within 1.5 months. The patient resumed taking verapamil as before and a remission occurred. Verapamil has been shown to inhibit TNF‐α and IL‐1β in vitro and in vivo. We hypothesize that verapamil inhibits the inflammatory process through the TNF‐α/IL‐1 pathway involved in the HS physiopathology. Compared to biologic agents as anti‐TNF‐α (adalimumab) and anti‐IL1 (anakinra), verapamil is safer and cheaper. Given its possible role on TNF‐α/IL‐1, verapamil may represent an alternative therapeutic option in mild and moderate HS.     

Differential potentiation by calcium antagonists of neuromuscular blockade induced by pancuronium and succinylcholine in cats in vivo

Summary The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non-depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2–40g/kg) and succinylcholine (6–200g/kg). The order of potency in increasing the effects of pancuronium was nicardipine d-cis diltiazem verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem verapamil nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved.     

The combination of Everolimus with Verapamil reduces ovarian weight and vascular permeability on ovarian hyperstimulation syndrome: a preclinical experimental randomized controlled study

The efficacy of pathways inhibition and the combined effect of Everolimus (mTOR inhibitor) and Verapamil (CYP3A inhibitor) in ovarian hyperstimulation syndrome (OHSS) need to be tested. Therefore, the impact of a leucotriene receptor antagonist, an anticoagulant, a GnRH antagonist as well as Everolimus plus Verapamil (at various doses and days of administration) on an OHSS rat model was tested. Sixty three female Wistar rats were randomly divided into seven groups. The control group received saline, while the OHSS group received rec-FSH for four consecutive days. The other five groups received rec-FSH for four days and Montelukast daily, Heparin daily, GnRH antagonist daily, Everolimus plus Verapamil in the last two days (half days group) and Everolimus plus Verapamil (half dose group) daily, respectively. All groups received also hCG at the fifth day. Significantly reduced ovarian weight was observed in the Everolimus plus Verapamil groups (half days and half-dose groups) and the Montelukast group compared to the OHSS group (p?=?0.001 and p?=?0.001, respectively). The vascular permeability was significantly reduced in the Everolimus plus Verapamil group (half dose group) and the GnRH antagonist group compared to the OHSS group (p?p?=?0.011, respectively). However, estradiol and progesterone levels did not differ significantly between the groups. Studying the inhibition of different pathways, we concluded that the co-administration of Everolimus and Verapamil (at half dose) is beneficial for reducing ovarian weight and vascular permeability in an OHSS animal model.     

The role of α<Subscript>1</Subscript>-and β-adrenoceptors in initiation and development of thermoregulatory reactions during fast and slow cooling

Ionophoretic application of α₁-and β-adrenoceptor blockers into the skin produces no effect on the parameters of thermal homeostasis under thermoneutral conditions. α₁-Adrenoblocker verapamil inhibits cold shivering during fast and slow cold exposure; it elevates the temperature threshold and moderates the vasoconstrictor response during rapid cooling. These changes are accompanied by a compensatory decrease in the threshold and stimulation of non-shivering thermogenesis. Application of non-selective β-blocker propranolol had no effect on the temperature thresholds of the thermoregulatory reactions, but augmented the maximum amplitude of shivering during both cooling protocols, thereby compensating the decrease in non-shivering thermogenesis. In the whole organism, block of one type adrenoceptors during cold exposure is accompanied by activation of the compensatory mechanisms mediated by adrenoceptors of the other type. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 259–262, March, 2008     

多奈哌齐与维拉帕米对大鼠阿尔茨海默病的干预研究

目的探讨多奈哌齐与维拉帕米对阿尔茨海默病(AD)大鼠学习记忆能力、脑组织一氧化氮(NO)和一氧化氮合酶(NOS)浓度的影响。方法 SAD大鼠40只,随机分为假手术组、模型组、多奈哌齐组和联合用药组。采用5μl Aβ1-40(2μg/μl)右侧海马区立体定向微量注射法制备大鼠AD模型,通过Morris水迷宫和三筒互通脑功能仪检测大鼠学习记忆变化,采用生化方分光光度法检测大鼠海马及大脑皮层中NO、NOS的含量。用多奈哌齐与维拉帕米以灌胃方法对模型大鼠进行干预,观察其实验效果。结果模型组较假手术组学习记忆能力显著降低,海马及大脑皮层NO、NBOS含量显著升高;多奈哌齐组和联合用药组较模型组学习记忆能力有所升高(P<0.05),海马及大脑皮层NO含量及NOS活性均有所降低(P<0.05)。其中联合用药组有些指标与模型组有差异显著(P<0.01)。结论用Aβ1-40右侧海马区立体定向微量注射法可建立AD动物模型,多奈哌齐与维拉帕米可改善AD模型大鼠的学习记忆,降低海马及大脑皮质NO和NOS含量,并且两药联合使用效果显著。     

The effects of verapamil and heparin co-administration on sperm parameters and oxidative stress in prevention of testicular torsion/detorsion damage in rats

In this research, the impacts of combined administration of verapamil and heparin on testicular torsion damage were examined. In this experimental study, 30 sexually mature male Wistar albino rats were divided into five equal groups haphazardly (n = 6): Group 1 was the sham group. In group 2, a 2-hr testicular torsion was induced, and thereafter, detorsion was done. Rats in group 3 and group 4 experienced an identical surgical procedure like group 2, but verapamil and heparin were administered in 0.3 mg/kg and 800 IU/kg doses respectively, and in group 5, a combination of verapamil and heparin were administered. Intraperitoneal drug injection in all treatment groups was done 30 min before testicular detorsion. Testicular torsion significantly changed sperm parameters, oxidative stress biomarkers and Cosentino's histological score compared to the sham group (p < .05). All treatment groups reduced testicular damage by decreasing oxidative stress and improving sperm parameters, but heparin and co-administration of verapamil and heparin were significantly better than verapamil injection alone. However, heparin injected group was more effective than other treatment groups (p < .05). Overall, an anticoagulant like heparin is more effective than a calcium channel blocker such as verapamil, and it is more likely to reduce testicular torsion injuries.     

地塞米松诱发白内障及维拉帕米阻断的研究

目的　探查地塞米松与晶状体组织间的作用途径 ,以维拉帕米 (Verapamil)探查Ca 离子在地塞米松诱发白内障过程中的作用。方法　 80只鸡胚随机分为 :空白对照组、地塞米松实验组和地塞米松联合维拉帕米实验组。两实验组鸡胚在施加药物后 2 4小时摘出晶状体 ,拍照记录晶状体浑浊度 ;Westernblotting分析鸡胚晶状体组织中地塞米松受体的表达 ;原子吸收光谱分析晶状体组织内Ca 、Mg 、Fe 含量的变化。结果　鸡胚晶状体组织中无地塞米松受体表达 ;地塞米松联合维拉帕米实验组鸡胚晶状体浑浊程度以及晶状体组织中Ca 的含量均低于地塞米松实验组 (P <0 .0 5 )。结论　地塞米松对晶状体组织的作用途径是间接的非特异性受体模式 ;Ca 对这一过程具有重要的介导作用 ;维拉帕米可以抑制晶状体组织中Ca 含量的积累并降低其浑浊程度。     

Simultaneous occurrence of ipsilateral cluster headache and chronic paroxysmal hemicrania: a case report

A 42-year-old man came to our headache unit in October 1995 complaining of recurrent attacks of headache, which had begun in February 1991. Chronic cluster headache was diagnosed, and he was given verapamil, 360 mg per day. The attacks ceased in the following months and verapamil was stopped in March 1996. In May 1997, a recurrence of the attacks required the readministration of verapamil, 360 mg per day. The attacks decreased (one to three per week), but after 2 months the patient reported a worsening in his condition due to the appearance of shorter attacks, which were diagnosed as chronic paroxysmal hemicrania. The administration of indomethacin, 225 mg per day, resulted in the disappearance of the short attacks. The concomitant occurrence of attacks of cluster headache and chronic paroxysmal hemicrania suggests the presence of shared factors in the pathophysiology of the two forms of headache. This hypothesis is supported by previous reports in the literature.     

The action of different coronary active drugs on intraand extravascular components of local myocardial perfusion

Summary In isolated guinea pig hearts epicardial perfusion was estimated by analysis of the transit profile of different fluorescence indicators. Several coronary dilating agents were tested with regard to their influence on local perfusion kinetics revealing distinct patterns of microcirculatory drug action.Supported by the Deutsche Forschungsgemeinschaft (SFB 68 A 18)