Recombinant streptokinase vs phenylephrine-based suppositories in acute hemorrhoids, randomized, controlled trial(THERESA-3)

AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) and phenylephrine-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(14 sites), randomized(1:1), open, parallel groups, active controlled trial was done. After inclusion, subjects with acute symptoms of hemorrhoids, who gave their written, informed consent to participate, were centrally randomized to receive, as outpatients, rSK(200000 IU) or 0.25% phenylephrine suppositories, which had different organoleptic characteristics. Treatment was administered by the rectal route, one unit every 6 h during 48 h for rSK, and up to a maximum of 5 d(20 suppositories) for phenylephrine. Evaluations were performed at 3, 5 and 10 d postinclusion. The main end-point was the 5th-day complete clinical response(disappearance of pain and edema, and ≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were evaluated too. RESULTS: 5thday complete response rates were 83/110(75.5%) and 36/110(32.7%) with rSK and phenylephrine suppositories, respectively. This 42.7% difference(95%CI: 30.5-54.2) was highly significant(P < 0.001). The advantage was detected since the early 3rdday evaluation(37.3% vs 6.4% for the rSK and active control groups, respectively; P < 0.001) and was kept even at the late 10thday assessment(83.6% vs 58.2% for rSK and phenylephrine, respectively; P < 0.001). Time for complete response was significantly shorter(P = 0.031; log-rank test) in the rSK group(median: 4.9 d; 95%CI: 4.8-5.0) with respect to the active control(median: 9.8 d; 95%CI: 9.8-10.0). Thrombectomy was necessary in 1/59 and 8/57 patients with baseline thrombosis in the rSK and phenylephrine groups, respectively(P = 0.016). There were no adverse events attributable to the experimental treatment. CONCLUSION: rSK suppositories showed a significant advantage over a widely used over-the-counter phen-ylephrine preparation for the treatment of acute hemorrhoidal illness, with an adequate safety profile.

Recombinant streptokinase vs hydrocortisone suppositories in acute hemorrhoids:A randomized controlled trial

AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written,informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h(first 3 units)and afterwards every 12 h until 8 administrations were completed(schedule A), one unit every 8 h until 6 units were completed(schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5,and 10 d post-inclusion. The main end-point was the 5thday response(disappearance of pain and bleeding, and≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170(91.8%; 95%CI:87.3-96.2), 155/170(91.2%; 95%CI: 86.6%-95.7%),and 46/170(27.1%; 95%CI: 20.1%-34.0%) with rSK(schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9%differences(95%CI: 56.7%-72.2% and 55.7%-72.0%)were highly significant(P < 0.001). This advantage was detected since the early 3rd day evaluation(68.8% and64.1% vs 7.1% for the rSK and active control groups,respectively; P < 0.001) and was maintained even at the late 10 th day assessment(97.1% and 93.5% vs67.1% for rSK and hydrocortisone acetate, respectively;P < 0.001). Time to response was 3 d(95%CI: 2.9-3.1)for both rSK groups and 10 d(95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant(P < 0.001). All subgroup stratified analyses(with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively(P < 0.001). There were no adverse events attributable to the experimental treatment.CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile.

Study of Adverse Events of Streptokinase Therapy in Patients with Acute ST Elevation Myocardial Infarction

Background: Despite of different adverse events, streptokinase (SK) is widely used to treat patients presented with acute ST segment elevation myocardial infarction. Objective: The purpose of the present study was to observe different adverse events in patients of acute ST segment elevation myocardial infarction receiving SK infusion. Methodology: This cross-sectional type of analytic observational study was carried out in the inpatient department of Cardiology at National Institute of Cardiovascular Diseases, Dhaka, Bangladesh from December 23rd 2019 to February 22nd 2020 for a period of two (2) months. All patients diagnosed as acute ST segment elevation myocardial infarction receiving SK were included in the present study. Adverse events were documented through completing a questionnaire by reviewing the records in the medical file as well as interviewing with the patients. Result: In this study, 43 (26.2%) patients developed different types of adverse events and 121 (73.8%) had no complications following SK infusion. The most common adverse event was hypotension i.e. 26 (60.4%) and other adverse events were bleeding 8 (4.8%) and allergic reaction 7 (4.2%). Statistically significant higher rate of adverse events occurred in diabetic, hypertensive and dyslipidemia group which was 26 (56.5%) Vs. 17 (14.4%), p = 0.000, 37 (36.6%) Vs. 06 (09.5%), p = 0.000 and 18 (54.5%) Vs. 25 (19.1%), p = 0.000 respectively. The independent factors for the development of adverse events were smoking {OR: 5.1 with 95% CI (1.7 to 15.1), p = 0.003}, diabetes {OR: 14.9 with 95% CI (5.0 to 44.8), p = 0.000}, hypertension {OR: 5.1with 95% CI (1.7 to 15.1), p = 0.003} and dyslipidemia {OR: 4.6 with 95% CI (1.5 to 13.7), p = 0.007}. Conclusion: Streptokinase infusion was associated with different adverse events. Among them the commonest one was hypotension and other less common events were minor bleeding and minor allergic reaction. The adverse events were more frequently documented in patients who were smoker, diabetic, hypertensive and dyslipidemic.

A comparative study of intravenous acelerated streptokinase dose regimen with conventional dose regimen for coronary thrombolysis

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Strain improvement, optimization and purification studies for enhanced production of streptokinase from Streptococcus uberis TNA-M1

BACKGROUND： Screening of isolates for their potency to produce streptokinase was an important criterion of this research. The current study emphasizes the strain improvement, optimization and purification studies for enhanced production of streptokinase from Streptococcus uberis TNA-M1 isolated from bovine milk. METHODS： The study was carried out on samples collected from milk sample. Primary screening and characterization is used as an excellent source for the isolation of 13-hemolytic organisms. Strain improvement was done by both physical ＆ chemical mutagenesis. The enzyme activity was checked by clot lysis assay and confirmed by fibrin plate method. The partially purified and crude enzyme were analysed by high-performance liquid chromatography. Molecular weight ＆ enzyme purity was checked by SDS -PAGE, further confirmed by fibrin zymography. RESULTS： Out of the 3 isolated strains, only one isolate expressed 13-haemolysis with streptokinase （SK） activity. Based on the results of radial caseinolytic assay and blood clot dissolving assay, isolate TNA-M1 demonstrated the highest streptokinase activity. Based on morphological, biochemical and molecular characterization, it was identified as Streptococcus uberis and the strain was named as Streptococcus uberis TNA-M1. The results indicated that ultra-violet （UV） and ethyl methane sulfonate （EMS） were effective mutagenic agents for strain improvement of Streptococcus uberis TNA-M1 and enhanced SK productivity. HPLC analysis was performed in order to confirm the presence of streptokinase with the similar retention time （0.875 min） with its standard （0.854） min. SDS-PAGE of the enzyme showed protein band of approximately 47 kDa and confirmed by fibrin zymography. It exhibited fibrinolytic activity, which was more potent than other fibrinolytic enzymes. Glucose and peptone were recorded to be the optimum carbon and nitrogen sources respectively. CONCLUSION： Thus this study presents its novelty by highlighting the potential of Streptococcus uberis TNA-M1 as a significant source for the production of fibrinolytic enzymes.

Phytochemical and in vitro biological investigations of methanolic extracts of Enhydra fluctuans Lour

Objective:To study the phytochemical and biological properties(antioxidant,anthelmintic and thrombolytic)of methanolic extracts of Enhydra fluctuant Lour.,a plant belonging to the Asteraceae family.Methods:The phytochemical evaluation was carried out by qualitative analysis.In vitro antioxidant activity of extract was studied using free radical scavenging assay,ability of reduction,total phenol and total flavonoid contents determination assays.The anthelmintic activity was determined using paralysis and death time of Pheretima posthuma(earthworm)and thrombolytic activity by clot disruption assay.Results:The phytochemical evaluation showed significant presence of flavonoids,triterpenes,carbohydrate,reducing sugars,saponins,phenols,diterpenes,protein and tannin.The antioxidant activity was found significant[IC_(50)(135.20±036)μg/mL]as compared to ascorbic acid[(130.00±0.76)μg/mL].The reducing power was increased with concentration.Total phenol and total flavonoid contents were(153.08±0.38)mg/mL and(172.04±0.56)mg/mL respectively.The paralysis and death time of earthworms for different concentrations of extract were determined and compared with albendazole.The results showed that 10 mg/mL of the crude extract had similar effect with albendazole.Additionally,the crude extract showed a concentration depended relationship with its anthelmintic property.The clot lysis activity of crude extract was compared to the standard streptokinase's clot lysis(40.13%)activity and found significant(31%).Conclusions:The study proves that the crude methanolic extract of Enhydra fluctuant Lour,has significant antioxidant,anthelmintic and thrombolytic activity containing wide range of phytochemicals.

In-vitro comparative study of cytotoxic and thrombolytic effects of methanolic extract of Cissus pentagona and Thunbergia grandiflora(Roxb.)leaves

Objective:To compare cytotoxic and thrombolytic activity of crude methanolic extract of Cissus pentagona(C.pentagona)and Thunbergia grandiflora Roxb.(T.grandiflora)leaves.Methods:The screening of cytotoxic activity was done by using brine shrimp lethality bioassay while the thrombolytic activity was evaluated by using the in vitro clot lysis model.In brief,venous blood from five healthy volunteers was allowed to form clots which were weighed and treated with the tested plant materials to disrupt the clots.Weight of clot before and after treatment provided a percentage of clot lysis and the results with streptokinase as positive control and water as negative control were compared.Results:Moderate cytotoxicity was found for both methanol extracts,and it was compared with the standard drug vincristine sulfate in the brine shrimp bioassay.In the present study,the LC50 values of the methanol crude extract of C.pentagona as well as T.grandiflora and vincristine sulfate were 291.33,243.37 and 12.59μg/mL,respectively.In thrombolytic study,it was found that C.pentagona and T.grandiflora showed(24.27±2.61)%and(19.56±2.98)%of clot lysis,respectively.Among the herbs studied,C.pentagona showed very significant(P<0.001)percentage of clot lysis than T.grandiflora,compared with reference drug streptokinase[(63.54±2.61)%].Conclusions:The results of the study demonstrated that the leaf of the plants contains preliminary cytotoxic effect on brine shrimp and promising thrombolytic activity in vitro when it is tested on human blood.However,further study is needed to evaluate its potential as a thrombolytic agent.

Relief from vascular occlusion using photothermal ablation of tlhrombus with a multimodal perspective

Fibrinolytic therapy for arterial or venous thrombotic disorders involves the systemic administration of thrombolytics such as streptokinase, which is associated with serious bleeding complications. With this study, we provide a proof-of-concept of photothermal thrombus ablation with gold nanorods exposed to near-infrared irradiation, both in vitro using materials generated from purified fibrinogen or plasma and in vivo in murine blood vessels. This is the first report of the application of photothermal therapy as an anti-thrombotic measure. Remarkably, the addition of streptokinase had a multimodal additive effect with regard to acceleration of photothermal lysis of thrombi even at a dose significantly below the therapeutic concentration, thus minimizing the life- threatening side effects and adverse complications. This combinatorial approach exhibits great promise for lysing pathological clots while effectively overcoming the drawbacks of existing therapies.