The effects of hemocoagulase in injectable form (hemocoagulating enzymatic fraction of South American snake Bothrops jararaca venom provided by Ravizza) on the control of intraocular bleeding during vitreous surgery were evaluated in rabbit eyes. Intraocular infusion solution with hemocoagulase (1 NIH thrombin unit/100 ml of BSS plus) significantly reduced the bleeding time. Electroretinogram b-wave and electroretinogram c-wave showed no abnormality. Infusate with hemocoagulase (1 NIH thrombin unit/100 ml of BSS plus) is not toxic to retinal tissue and appeared to be a useful agent for the control of intraocular bleeding during vitreous surgery.
Animals ; Batroxobin/*administration & dosage ; Eye Hemorrhage/*prevention & control ; Injections ; Rabbits ; Serine Endopeptidases/*administration & dosage ; *Vitrectomy/adverse effects

PURPOSE: The purpose of this study was to determine the pharmacogenetic effects of complement factor H (CFH) Y402H, LOC387715 and high-temperature requirement factor A1 (HTRA1) genotypes on the treatment of exudative age-related macular degeneration (AMD) by intravitreal bevacizumab injection in a Korean population. METHODS: Seventy-five patients diagnosed with exudative AMD were treated with intravitreal bevacizumab (2.5 mg) monotherapy. All patients received three initial intravitreal bevacizumab injections every four weeks and were then treated "as needed" based on clinical findings, optical coherence tomography and fluorescein angiography during the 12 month follow-up period after the third injection. RESULTS: The difference in visual acuity improvement among the three genotypes of LOC387715 were statistically significant at six months post-treatment (logarithm of the minimum angle of resolution; TT, 0.346; GT, 0.264; GG, 0.188; p = 0.037). Among the LOC387715 genotypes, the number of additional injections was lower in patients who had the risk T allele (GG, 2.143; GT, 2.000; TT, 1.575; p = 0.064). There was no significant difference between visual acuity and central macular thickness change in the CFH Y402H polymorphism group during the 12 month follow-up period. However, the TC group of CFH Y402H required more additional bevacizumab injections than the TT group (TT, 1.517; TC, 3.363; p = 0.020). CONCLUSIONS: This study demonstrated that different LOC387715/HTRA1 genotypes resulted in different bevacizumab treatment responses on exudative AMD. Patients with the risk allele had an improved treatment response and less need for additional injections. However, patients with the CFH Y402H risk allele needed more additional injections of bevacizumab in order to improve visual acuity. This study illustrates how pharmacogenetic factors may help determine treatment modality and dosing. This could ultimately provide basic data for 'personalized medicine' in AMD.
Aged ; Alleles ; Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Antibodies, Monoclonal, Humanized/*administration & dosage/therapeutic use ; DNA/*genetics ; Female ; Follow-Up Studies ; Genotype ; Humans ; Intravitreal Injections ; Macular Degeneration/drug therapy/epidemiology/*genetics ; Male ; Pharmacogenetics/*methods ; *Polymorphism, Genetic ; Retrospective Studies ; Serine Endopeptidases/*genetics/metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity

OBJECTIVETo investigate the association between insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and the A/B polymorphism of the chymase (CMA) gene with regression of left ventricular hypertrophy (LVH) in patients with essential hypertension and left ventricular hypertrophy. The study subjects had been participants in along-term trial of therapy with an ACE inhibitor.

METHODSFollow-up data of 157 patients with essential hypertension and left ventricular hypertrophy were collected. DNA fragments of ACE gene and CMA gene were amplified by PCR and analysed by RFLP. LVDd, IVST and LVPWT were measured by Ultrasonic Cardiogram (UCG).

RESULTS(1) When long-term treatment with Benazepril was carried out, the blood pressure was markedly decreased and the heart rate was maintained steadily. (2) Regression of left ventricular hypertrophy was improved. (3) The magnitudes of regression of LVM and LVMI during therapy were greater in the DD group than in the II and ID group. No significant differences of other indices were found in the different genotype groups of ACE. (4) No significant differences of all indices were found in the different genotype groups of CMA. (5) No interaction appeared between the genotypes of the ACE and the genotypes of the CMA.

CONCLUSIONHypertensive patients with DD genotype were more likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than patients with other ACE genotypes. No evidence was found to support an association between CMA genotype and regression of LVH in those patients.

Adult ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Benzazepines ; administration & dosage ; therapeutic use ; Chymases ; Female ; Follow-Up Studies ; Genotype ; Humans ; Hypertension ; complications ; drug therapy ; genetics ; Hypertrophy, Left Ventricular ; drug therapy ; etiology ; genetics ; Male ; Peptidyl-Dipeptidase A ; biosynthesis ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Serine Endopeptidases ; biosynthesis ; genetics

OBJECTIVETo investigate the regulatory mechanisms of integrin α5 and β1 in osteoblast in the process of gingipains-induced apoptosis.

METHODSGingipains were isolated and purified from supernatants of Porphyromonas gingivalis W83 which was cultured under standard anaerobic conditions. MC3T3-E1 was challenged with or without 8.3480 U/L gingipains for 48 h and apoptosis was examined by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (TUNEL-DAPI) staining. The expression of integrin α5 and β1 was analyzed by Western blotting after MC3T3-E1 was treated under different conditions.

RESULTSArginine-specific proteinases(Rgp) activity was (41.74 ± 2.11) U/L and lysine-specific proteinase(Kgp) was (1.02 ± 0.25) U/L.Gingipains induced MC3T3-E1 cells apoptosis after 48 h. Compared with control group, expression of integrin α5 and β1 was down-regulated by gingipains in a time-dependent manner within short periods ( ≤ 72 h), integrin α5 and β1 relative expression was (0.485 ± 0.039),(0.504 ± 0.002) at 48 h,(0.398 ± 0.058),(0.179 ± 0.001) at 72 h respectively (P < 0.05). After 72 h, integrin α5 expression in MC3T3-E1 cells was stable compared with control group while integrin β1 was still lower(control group:1.000 ± 0.000, 96 h:0.604 ± 0.003, 120 h: 0.357 ± 0.002) (P < 0.05). Proteinase inhibitor tosyl- L- lysine-chloromethyl-ketone(TLCK) effectively blocked the activity of gingipain and inhibited down-regulation of integrin α5 and β1 induced by gingipains from (0.398 ± 0.058,0.179 ± 0.001 ) to (0.781 ± 0.012, 0.857 ± 0.060) (P < 0.05). TLCK alone did not have any effect on integrin α5 and β1(P > 0.05). Gingipains also decreased integrin α5 and β1 in a dose-dependent manner.When cells were treated with 20.8700 U/L gingipains, integrin α5 and β1 relative expression reached to the lowest(0.105 ± 0.004,0.020 ± 0.000) (P < 0.05).

CONCLUSIONSGingipains inhibited the expression of integrin α5 and β1 in a time- and dose- dependent manner in osteoblasts in the process of apoptosis, which may not be mediated by direct proteolytic effect.

Adhesins, Bacterial ; administration & dosage ; isolation & purification ; pharmacology ; Animals ; Apoptosis ; drug effects ; Cysteine Endopeptidases ; administration & dosage ; isolation & purification ; pharmacology ; Dose-Response Relationship, Drug ; Down-Regulation ; Integrin alpha5 ; metabolism ; Integrin beta1 ; metabolism ; Mice ; Osteoblasts ; cytology ; metabolism ; Porphyromonas gingivalis ; chemistry ; Serine Proteinase Inhibitors ; pharmacology ; Time Factors ; Tosyllysine Chloromethyl Ketone ; pharmacology