Tranexamic acid use in the setting of ACE inhibitor induced angioedema.

Tranexamic acid (TXA) is an antifibrinolytic agent which reduces bradykinin production through its blockade of the conversion of plasminogen to plasmin and subsequently pre-kallikrein to kallikrein. It has been utilized in angiotensin converting enzyme (ACE) inhibitor-induced angioedema (ACEi-AE) in small case reports and series however overall data is limited. This report describes a patient who historically received TXA for ACEi-AE and represented with ACEi-AE after an accidental exposure and was successfully treated with TXA again. This case suggests TXA may be a safe and effective treatment option for ACEi-AE.

Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study).

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

Edema angioneurótico hereditario / Hereditary angioneurotic edema

Se realiza una revisión del tema edema angioneurótico hereditario. Después de una introducción histórica se considera el sistema del complemento, el sistema de las cininas, los inhibidores de las proteasas hemáticas derivadas del plasminógeno y la vinculación entre ambos. Se consideran también los avances últimos en lo que a citogenética molecular se refiere. Se presentan las diferentes formas clínicas de los edemas angioneuróticos hereditarios, así como sus diferencias clínico-laboratoriales. Se hace una valoración de los tratamientos sustitutivos y profilácticos. Se expone el estudio de tres casos clínicos observados en el lapso de 30 años de práctica dermatológica.

Hageman factor and kallikrein in pathogenesis of senile cataracts and the pseudoexfoliation syndrome.

It is thought that dystrophic changes in the human aging anterior eye are due to lipid peroxidation in both the cortical and nuclear structures of the lens under the conditions of ischemia. These changes are often accompanied by only lens opacification (senile cataract-SC) or by formation of amorphous or fibrillar deposits in anterior eye, disturbances of eye hydrodynamics and lens opacification (pseudoexfoliation syndrome-PES). Our results suggest that the main reason of dystrophic changes in the tissues of the aging anterior eye is the disturbance of the haemato-ophthalmic barrier and that the plasma kallikrein-kinin system takes part in this disturbance. Penetration of plasma proteins, such as C-reactive protein, complement components, immunoglobulins and coagulation factors, from plasma into the aqueous humor is responsible for damaging epithelial structures of anterior eye and formation of pseudoexfoliative material. Using ELISA, the C-reactive protein, IgG and IgM antigens have been shown to localize on the surface of the opaque lenses. Presence of these complement binding proteins in the superficial lens structures as well as the high C3a concentration in the aqueous humor substantiates the pathogenic role of complement activation in the lenticular epithelium upon cataract and PES formation.

Characterisation of a novel series of aprotinin-derived anticoagulants. II. Comparative antithrombotic effects on primary thrombus formation in vivo.

Upon vascular damage platelet activation and blood coagulation are initiated. Interference at the initial level of the activation of the coagulation cascade can result in effective inhibition of thrombus formation. The in vivo antithrombotic properties of a series of bovine pancreatic trypsin inhibitor mutants (BPTI, aprotinin) 4C2, 7L22, 5L15, 5L15-PEG, 6L15 and 5L84, as described in the accompanying paper, with a combined inhibitory activity on factor Xa, factor VIIa-tissue factor complex, factor XIa and plasma kallikrein were compared to rTAP, r-hirudin, heparin and enoxaparin in a platelet rich thrombosis model in hamsters. Platelet dependent thrombus deposition was quantified by dedicated image analysis after transillumination of the femoral vein to which a standardised vascular trauma was applied. After increasing intravenous bolus injections all tested agents, except for aprotinin, induced a dose dependent decrease of thrombus formation and a concomitant prolongation of the aPTT. From the linear correlation between these two parameters it was found that 5 out of the 6 tested aprotinin analogues, rTAP and r-hirudin completely inhibited thrombus formation at a therapeutical (2- to 3-fold) aPTT prolongation while 4C2, heparin and enoxaparin only inhibited thrombus formation for 40 to 50 percent at a 2-fold aPTT prolongation. Based on the calculated IC50 values for thrombus formation rTAP was found to be the most active compound in this model. It is concluded that acceptable interference at the initial level of the blood coagulation, e.g. within a therapeutical aPTT prolongation, can significantly inhibit platelet deposition at a site of vascular injury.

[Basic principles of drug therapy in andrology. Experiences of 40 years andrologic treatment]. / Grundsätze der medikamentösen Therapie in der Andrologie. Erfahrungen in 40 Jahren andrologischer Tätigkeit.

Medical treatment of fertility disorders in the male must be based on a definitive diagnostic work-up. Before initiating therapy, all possible endogenous and exogenous injurious factors, including a varicocele and the use of nicotine and a variety of medications, must first be excluded. A further important medical measure is actively involving the patient in the treatment plan, which is of particular importance with respect to the above-mentioned points. Another major role in the management of childless couples is andrological/gynecological cooperation. For the treatment of disorders of morphological quality, androgens are to be given preference, while disorders of motility in the presence of largely normal morphological quality respond well to kallikrein.

[The efficacy and tolerance of orally administered kallikrein in patients with essential arterial hypertension]. / Efficacia e tollerabilità della somministrazione orale di callicreina in pazienti affetti da ipertensione arteriosa essenziale.

Since the reduced kallikrein excretion demonstrated in essential hypertension suggested the possibility of an impairment in the renal kallikrein-kinin system, we decided to evaluate the efficacy and safety of oral kallikrein administration (glandular kallikrein derived from porcine pancreas) in 30 essential hypertensive subjects (21 males, 9 females, age range 34-62 years). Twenty subjects took 150 IU kallikrein t.i.d. for eight days; during this period their sodium intake remained normal (120 mEq Na+/die). Ten subjects took placebo. After the trial period, urinary kallikrein in the active group increased from 0.9 +/- 0.4 U/24 h (normal value greater than 1.2 U/24 h) to 1.6 +/- 1 U/24 h (p less than 0.05); systolic and diastolic blood pressure decreased respectively from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg (p less than 0.01) and from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg (p less than 0.025); urinary sodium and potassium excretion increased respectively from 96.7 +/- 17 mEq/24 h to 119.1 +/- 32.3 mEq/24 h (p less than 0.05) and from 36.7 +/- 11 mEq/24 h to 43.5 +/- 12.8 mEq/24 h (p less than 0.05). One patient in the kallikrein group suffered a transient episode of gastric pain. No modifications of the parameters evaluated were observed in the placebo group. We conclude that kallikrein has a mild hypotensive effect in hypertensive subjects and is generally well-tolerated. Its antihypertensive effect is probably due to the sodiuretic action of the substance.

Treatment of idiopathic oligozoospermia by kallikrein: results of a double-blind study.

Ninety subfertile men with idiopathic oligozoospermia were treated orally with either 600 units porcine pancreatic kallikrein or placebo daily for 7 wk. Kallikrein caused an increase in the number of spermatozoa (3.1 X 10(7) with a maximum 2--3 mo after onset of therapy. There was an improvement of the quantitative and qualitative sperm motility with a maximum at the end of treatment. Five months after onset of therapy, pretreatment values were regained. There were no major side effects. Conception rates within a period of 1 yr were 16% for placebo and 38% for kallikrein.

[Initial results in the treatment of male fertility disorders with kallikrein: asthenozoospermia]. / Erste Ergebnisse der Behandlung von männlichen Fertilitätsstörungen mit Kallikrein: Asthenozoospermie

30 patients with asthenozoospermia were treated with kallikrein a kinin-liberating proteinase over a period of seven weeks. During parenteral and oral application of kalikrein and after medication within an observation period of 3 months a significant increase of the quantitative and qualitative sperm motility was found. Parenteral application of kallikrein led to a significant increase of the number of spermatozoa 3 months after beginning of the kallikrein therapy. Other semen parameters were not influenced. No side-effects were observed.