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U istraživanju su analizirani serumi 10955 ispitanika na protutijela ANA tijekom rutinske dijagnostičke obrade metodom imunofluorescencije (IF) na stanicama HEp-2 te su klasificirani u 30 zasebnih obrazaca prema važećim smjernicama. 22 obrasca klasificirana su kao rijetki. Od ukupnog broja seruma, ANA su potvrđena u 4107 (37,5 %) ispitanika, od kojih 2364 (57,6 %) uobičajenih i 1743 (42,4 %) rijetkih obrazaca IF. Najveći udio rijetkih obrazaca IF u svim ispitivanim uzorcima činili su obrasci AC-2, AC-15, AC19 i AC-29 (svaki > 1 %), a najmanji udio AC-17 i AC-24 s udjelom < 0,1 %. Specifična protutijela određena Theradiag FIDIS™ panelom nađena su kod 48,4 % uobičajenih obrazaca IF i 46,1 % rijetkih obrazaca IF. Općenito, ispitanici s rijetkim obrascima IF nisu se znatno razlikovali od kontrolne skupine s uobičajenim obrascima IF u odnosu na spol, dob, prisutnost ili broj specifičnih protutijela, kao ni prema skupinama kliničkih dijagnoza; iznimka su jetrene bolesti koje su bile učestalije u ispitanika s rijetkim obrascima IF. Analiza pojedinačnih rijetkih obrazaca IF u odnosu na kontrolnu skupinu pokazala je velike razlike u njihovoj učestalosti i kliničko-laboratorijskim karakteristikama. Veći udio muškaraca nađen je među obrascima AC-9, AC-15, AC-16, AC-19, AC-22, AC-24 i AC-25, dok su ispitanici s AC-2, AC-7, AC-10, AC-13 i AC-24 bili znatno mlađi. Specifična protutijela bila su manje učestala u obrascima AC-2, AC-9, AC-10, AC-15, AC-22 i AC-25, a učestalija u AC-13, AC-19 i AC-29. Dijagnoze sistemskih autoimunosnih bolesti bile su rjeđe u ispitanika s obrascima AC-22, AC-23 i AC-27, a učestalije u AC-13 i AC-18. Dijagnoze jetrenih bolesti bile su češće u obrascima AC-6, AC-11, AC-12, AC-15, AC-17 i AC-22, a tumorske u obrascima AC-12 i AC-16. Zaključno, rijetki obrasci IF ne smiju se zanemariti kod dijagnostike ANA jer mogu biti povezani s određenom kliničkom patologijom i usmjeriti daljnji dijagnostički postupak., Sera of 10955 patients were routinely analyzed for presence of ANA using immunofluorescence on HEp-2 cells, and classified into 29 patterns as per international guidelines. 22 patterns were deemed uncommon. In total, ANA were found in 4107 sera, of which 2364 were common, 1743 uncommon. Specific autoantibodies determined using Theradiag FIDIS™ panel were found in 48.4% common and 46.1% uncommon patterns. Generally, common and uncommon patterns were similar regarding sex, age, presence and number of antibodies, or clinical diagnoses. Male patients were more common in AC-9, AC-15, AC-16, AC-19, AC-22, AC-24, AC-25, and AC-26 patterns, while patients with AC-2, AC-7, AC-10, AC-13, and AC-24 were substantially younger. There were fewer specific antibodies in AC-2, AC-9, AC-10, AC-15, AC-22, and AC-25 patterns, and more in AC-13, AC-19 i AC-29. Diagnoses of systemic autoimmune rheumatic diseases were less common in patients with AC-22, AC-23, and AC-27 patterns, and more common in case of AC-13 and AC-18 patterns. Liver diseases were more common in AC-6, AC-11, AC-12, AC-15, AC-17, and AC-22 patterns. Tumors were associated with AC-12 and AC-16 patterns. Uncommon ANA patterns mustn't be overlooked in ANA analysis, as they can be associated with certain pathology and influence the diagnostic procedure.

In the current report, the interaction of Al-doped carbon nanotubes (CNT) with carbazochrome, an anti-hemorrhagic or hemostatic agent, was investigated with the M06-2X functional and 6-31G* basis set. The global index including frontier molecular orbital energies, hardness, softness, chemical Gibbs energies and some parameters and NLO properties of Carbazochrome, Al doped CNT and complexes formed between their were calculated and evaluated. Electron localization function (ELF) calculations were performed to validate the essence of the formed bonding model progress along the interaction. It is obtained that polarizability of the complex are bigger than those of Carbazochrome and Al doped CNT. According to the maximum electron flow index, the electrophilicity power is increased by increasing the chemical potential, the decreasing chemical hardness. All obtained complexes are exergonic and thus thermodynamically favorable, Bu çalışmada, Al doplu karbon nanotüplerin (CNT)'nin anti-hemorajik veya hemostatik bir ajan olan karbazokrom ile etkileşimi, M06-2X fonksiyonel ve 6-31G* temel seti ile araştırıldı. Karbazokrom molekülü, Al doplu CNT ve aralarında oluşan komplekslerin sınır moleküler orbital enerjileri, sertlik, yumuşaklık, kimyasal Gibbs enerjisi gibi bazı parametreler ile NLO özelliklerini içeren global indeks hesaplandı ve değerlendirildi. Etkileşim boyunca oluşturulan bağ modeli ilerlemesinin özünü doğrulamak için elektron lokalizasyon fonksiyonu (ELF) hesaplamaları yapıldı. Kompleksin polarizebilitesinin Karbazokrom ve Al doplu CNT'den daha büyük olduğu elde edilmiştir. Maksimum elektron akış indeksine göre, artan kimyasal potansiyel ve azalan kimyasal sertlik ile elektrofilik gücü artar. Elde edilen tüm kompleksler ekzergoniktir ve bu nedenle termodinamik olarak uygundur.

Objective Carbazochrome sodium sulfonate (CSS) has been routinely used to treat bleeding; however, no study has examined the effect of CSS for gastrointestinal bleeding. Therefore, we aimed to investigate the effect of CSS for colonic diverticular bleeding. Methods We performed a nationwide observational study using the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for diverticular bleeding from July 2010 to March 2018. Patients who received CSS on the day of admission were defined as the CSS group, and those not receiving CSS were defined as the control group. The primary outcome was in-hospital mortality. Secondary outcomes were length of stay, total costs, and blood transfusion within 7 days of admission. Propensity score matching analyses were performed to compare outcomes between the two groups. Results A total of 59,965 patients met our eligibility criteria. Of these, 14,437 (24%) patients received CSS on the day of admission. One-to-one propensity score matching created 14,379 matched pairs. There was no significant difference in the in-hospital mortality between the CSS and control groups (0.6% vs. 0.5%, respectively; odds ratio: 0.96; 95% confidence interval: 0.72-1.29). The length of stay was longer in the CSS group than in the control group (11.4 vs. 11.0 days, respectively; difference: 0.44; 95% confidence interval: 0.14-0.73). There were no significant differences in the total costs or the proportion of patients receiving blood transfusion between the groups. Conclusions CSS may not reduce in-hospital mortality, length of stay, total costs, or the need for blood transfusion in patients with colonic diverticular bleeding.

Pelvic venous congestion (PC) is thought to be related to several diseases of the lower urinary tract (LUT). We examined the characteristics of the LUT in rats with PC. To create PC, female rats were anesthetized with isoflurane, and the bilateral common iliac veins and bilateral uterine veins were ligated. At 1-8 weeks after either ligation or sham surgery, we performed cystometry with or without administration of carbazochrome sodium sulfonate hydrate or propiverine hydrochloride, histologic examination of the bladder, blood flow imaging, assessment of locomotor activity, measurement of urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx), and the Evans blue dye extravasation test. PC elevated frequency of urination after 2-6 weeks, and caused a decrease of spontaneous locomotor activity. In addition, there was a decrease of bladder blood flow, an increase of bladder vascular permeability, an increase of urinary 8-OHdG, a decrease of urinary NOx, and mild inflammatory changes of the bladder. In rats with PC, frequency of urination was normalized by administration of propiverine or carbazochrome. Rats with PC may be used as a model of PC associated with high frequency of urination, and this model may be useful when developing treatment for LUT symptoms associated with PC.

The carbazochrome (3) solubility in solvent mixtures of DMF (N,N-dimethylformamide, 1) + methanol (2), DMF (1) + ethanol (2), DMF (1) + n-propanol (2), and dimethyl sulfoxide (DMSO, 1) + water (2) was measured by the static method within the temperature range from (278.15 to 318.15) K under atmospheric pressure, p = 101.0 kPa. The solubility of carbazochrome increased with rising mass fraction of DMF or DMSO and temperature. The Jouyban–Acree, van’t Hoff–Jouyban–Acree, and Apelblat–Jouyban–Acree models were used to correlate the obtained solubility, and the Apelblat–Jouyban–Acree model provided better correlation results. The parameters of preferential solvation (δx1,3) were acquired from the mixture properties with the method of inverse Kirkwood–Buff integrals. The values of δx1,3 changed nonlinearly with the DMF/DMSO (1) proportion in the studied mixed solvents. The carbazochrome was solvated preferentially by alcohol or water in alcohol or water-rich solutions and preferentially solvated by DMF/DMSO in...

The design of a cheap, simple, and handy sensing system for rapid quantitation of pharmaceuticals becomes mandatory to ease drug development procedures, quality control, health care, etc. This work describes a simple, innovative, and easily manufactured paper-based device using a correction pen as a plotter for hydrophobic/lipophobic barriers and graphene quantum dots for recognition and quantification of the hemostatic drug carbazochrome, via fluorescence turn-off mechanism mediated by the inner filter effect. A smartphone-based all-in-one device fitted with an inexpensive 365 nm flashlight as a UV light source and a free image processing software was developed for rapid and reliable interpretation of the fluorescence change from the paper-based device upon introduction of the drug. The simple and convenient steps permit the analysis of many samples in a very short time. The smartphone-based all-in-one device featured excellent sensitivity for carbazochrome with a limit of detection equals to 12 ng/detection zone and good %recovery (100.0 ± 0.4). The reliability of the device was ascertained by favorable statistical comparison with the analogous optimized conventional fluorimetry method and a reference HPLC method. The device has been successfully applied for versatile quantitation of carbazochrome in tablets and on manufacturing equipment surfaces with excellent recoveries. The device offers many green aspects that definitely assist the implementation of the sustainability concept to analytical laboratories. The cost-efficiency, reliability, and ease of fabrication as well as the greenness and user friendship qualify the device for wide application in low-income communities.

Embolic agents are crucial for trans-catheter arterial embolization (TAE) in the treatment of various unresectable malignant tumors. Although solid particles, liquid oils, and some polymeric hydrogels have proved their capacities for embolic therapies, the low efficiency, time sensitivity, and cytotoxicity are still considered as challenges. In this study, we developed a three-component dynamic self-healing hydrogel to overcome these limitations. With the help of the Schiff-base bonding, both glycol-chitosan and carbazochrome, containing amine groups, react with dibenzaldehyde-terminated poly(ethylene-glycol) (DF-PEG), forming the dynamic self-healing hydrogels under a mild condition within 200 s. 1H NMR and rheology test were used to characterize the Schiff-base formation and mechanical strength. Controlled-release of carbazochrome from different gelator concentrations of DF-PEG was also studied. Furthermore, in vivo evaluation of the embolization on rats showed the superior embolic effects of the injectable and self-healing hydrogel. Therefore, this new dynamic agent demonstrated the potential for application as a simple, inexpensive, and tunable embolic agent for cancer treatment and drug delivery system.

Aim We investigated whether the high-dose administration of tranilast could be used to create an animal model of interstitial cystitis (IC). Then, we used this model to assess the relationship between IC and changes in the vascular permeability of the bladder. Main methods Female rats were divided into the following 4 groups: a control group, a tranilast group, a carbazochrome group and a combination (tranilast + carbazochrome) group. Continuous cystometry, bladder distension, and the Evans blue dye extravasation test were performed 4 weeks after drug administration. Locomotor activity, the plasma TGF-β1 level, and collagen fibers in the bladder wall were also examined in the control and tranilast groups. Key findings The interval between bladder contractions was shorter and the leakage of Evans blue dye into the bladder wall was greater in the tranilast group than in the control group. Glomerulations of the bladder wall after bladder distention and thinning of the collagen fiber layer in the bladder were observed in the tranilast group. Locomotor activity in darkness and the plasma TGF-β1 level were both lower in the tranilast group than in the control group. In the combination group, the leakage of Evans blue dye was greater than in the control group; however, it was less prominent than in the tranilast group. Significance These results suggest that high-dose administration of tranilast to rats can create an IC-like rat model and that an increase in the vascular permeability of the bladder wall may be one cause of IC symptoms.

A 39-year-old man suffering from progressive dysarthria, gait disturbance, and sensorineural deafness for 2 years was admitted to our hospital. He scored 28 points on the mini-mental state examination. He had previously undergone surgery at 24 years and 39 years of age for a cerebellar tumor (pilocytic astrocytoma). Superficial siderosis (SS) was diagnosed based on bloody cerebrospinal fluid (CSF) and the findings of T2-weighted head MRI that revealed marginal hypointensity of the surface of the cerebellum, brainstem, and cerebral cortex. After intravenous infusion and the oral use of hemostatic drugs (carbazochrome, tranexamic acid), the CSF became watery clear and his condition improved. Hemostatic drug therapy should be considered for SS.

Background: Flavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination of troxerutin 150 mg plus carbazochrome (an oxidation product of epinephrine that enhances the microcirculatory tone) 1.5 mg has been shown to have a good efficacy and tolerability profile in nonsurgical patients with acute, uncomplicated hemorrhoids. A previous pilot study we carried out in 30 posthemorrhoidectomy patients showed that this combination was also effective and well tolerated in improving posthemorrhoidectomy symptoms. Objective: This study compared the efficacy and tolerability of troxerutin-carbazochrome active combination with placebo in the treatment of posthemorrhoidectomy symptoms. Methods: In this single-center, randomized, double-blind, placebo-controlled study, patients scheduled for hemorrhoidectomy were randomized to receive 1 of 2 treatments: troxerutin 150 mg plus carbazochrome 1.5 mg active combination or placebo IM in 3-mL ampules BID for 5 consecutive days after surgery, starting on the day of surgery. Efficacy parameters were assessed at baseline (T1), after the first administration (T2; day of surgery), day 2 after surgery (T3), and day 5 after surgery (T4). Efficacy parameters assessed included hemorrhoidal symptoms based on a visual analog scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; edema; analgesic intake, if any; time to restore physiologic defecation; photographs taken at T1 and T4 (in selected patients; not included here); and standard blood coagulation tests. Results: Sixty patients were enrolled (33 males, 27 females; mean age, 45.6 ± 7.4 years). Analysis between treatment groups revealed significant differences in mean total VAS scores at T3 and T4 ( P = 0.01 and P = 0.001, respectively) in favor of the active-combination group. Statistically significant between-group differences in scores for bleeding and pruritus at T3 and for bleeding, pruritus, and edema at T4 in favor of the active-combination group also were found ( P Conclusions: IM administration of troxerutin 150 mg plus carbazochrome 1.5 mg combination was effective, well tolerated, and superior to placebo in improving hemorrhoidal and postsurgical signs and symptoms in 5 days of treatment in this study population.

各種出血に対して止血は重要な処置である．動脈性の出血に対しては外科的な処置で対応することが基本となるが，oozing様の出血に対しては血管強化薬や局所止血薬が使用されることがある．以下に血管強化薬と局所止血薬の特徴を概説する．

Points(1) カルバゾクロムは毛細血管に作用して血管透過性亢進を抑制し，出血時間を短縮し止血作用を示す．(2) ビタミンCの投与によりビタミンC欠乏症（壊血病）は治療できる．(3) フィブリン接着剤は，フィブリノゲンがトロンビン，凝固第XIII因子，カルシウムの作用により架橋化フィブリンとなり，組織の接着・閉鎖作用を発揮する．(4) ゼラチン吸収性スポンジ，酸化セルロースはフィブリンと同等の止血効果をあらわす可吸収性止血薬である．(5) アドレナリンは血管を収縮させ局所止血作用を示す．

This study investigated the effect of carbazochrome sodium sulphonate (AC-17) on the accumulation of tissue-type plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) in culture medium of human umbilical vein endothelial cells (HUVEC). HUVEC were cultured in the presence of AC-17, and the concentration of t-PA:Ag and PAI-1:Ag in the medium was measured by an enzyme-linked immunoassay. AC-17, after 48 and 72 h incubation, significantly decreased the t-PA:Ag in the culture medium, while it had no significant effect on the PAI-1:Ag. The result of fibrin zymography was consistent with the result obtained by ELISA. It also revealed that all of the t-PA present in the culture medium formed complexes with PAI-1, indicating that AC-17 did not interfere with t-PA/PAI-1 complex formation. Furthermore, AC-17 did not inhibit the activities of t-PA and plasmin when measured by a fibrin plate method. These results suggest that AC-17 may modulate the fibrinolytic balance of blood through changing the function of endothelial cells, a new aspect of action of AC-17 as a haemostatic drug.

In patients receiving radical surgery for chronic paranasal sinusitis, we compared the hemostatic effects of Opthalm K® (carbazochrome 10mg, phytonadion 5mg and ascorbic acid 100mg), with that of combinations of any two of the three ingredients in a double-blind controlled trial. The study involved a total of 219 patients from 13 institutions, and the medications were compared in 211 patients after 8 had been withdrown because of ineligibility. The overall efficacy of the drugs was assessed on the basis of the decrease in bleeding time, and the reduction of intra-operative and of post-operative blood loss. The overall usefulness was judged from the overall efficacy plus the overall safety. Both of the efficacy and the usefulness of Opthalm K® were superior to those of the products combining only two of the three ingredients.

A sensitive, simple and selective spectrofluorimetric method for the reaction of carbazochrome (CBZC) and Eosin Y (EY) or Phloxine B (PB) in acidic medium is developed for the determination of carbazochrome in biological fluids, which gives a highly fluorescent derivative measured at 545 and 565 nm at excitation wavelengths of 301 and 305 nm. The fluorescence quenching extent (Δ F ) is proportional to the concentration of CBZC for CBZC–EY and CBZC–PB system at the range of 0.03–1.50 μg/mL and 0.08–1.25 μg/mL, respectively. The detection limit is 9.1 ng/mL for EY system and 22.7 ng/mL for PB system. The intra-day and inter-day reproducibility (RSD values) are less than 8.3% under three concentrations. Moreover, the affecting factors of fluorescence intensity of the product are carefully investigated and optimized, as well as the effect of coexisting substances. Judging from temperature, the Stern–Volmer plots and fluorescence emission decay curves, the quenching of fluorescence of EY and PB by CBZC is a static quenching process, caused by electrostatic attraction and aromatic stacking interaction.

Electronic database Medline, Embase, Cochrane Library and Lilacs were used to retrieve the clinical trials that will evaluate the various therapeutical options available for management of hemorrhagic dengue. Eight clinical studies were included. Supportive care and symptomatic treatment through hydration and aggressive fluid management, if hypotension develops in the course of disease, are the most important aids to improve survival. Treatment with corticosteroids such as methylprednisolone, hydrocortisone, carbazochorome sodium sulfonate (AC-17) and recombinant activated factor VII did not reduce mortality in children with hemorrhagic dengue. At present, no vaccine or effective antiviral treatment is available for the prevention or treatment of hemorrhagic dengue. © 2007 1999, Editorial Ciencias Médicas.

The effects of carbazochrome sodium sulfonate (AC-17), a capillary stabilizer, on pulmonary edema and dysfunction induced by ioxaglate, an ionic radiographic contrast medium, were evaluated in rats. The pulmonary edema was evaluated by the extravasation of intravenously injected Evans blue into lung tissues, while pulmonary dysfunction was determined by monitoring blood gasses including p O 2 . Ioxaglate (4 g I/kg, i.v.) caused a marked increase in vascular permeability and a decrease in arterial p O 2 . AC-17 reversed the ioxaglate-induced vascular hyperpermeability in a dose-dependent manner. In addition, AC-17 (10 mg/kg) significantly inhibited the decrease in arterial p O 2 . In isolated rat pulmonary mast cells, ioxaglate markedly enhanced the histamine release, which was not affected by AC-17. On the other hand, AC-17 did significantly blocked the hyperpermeability induced in cultured bovine endothelial cells by tryptase, thrombin and proteinase-activated receptor-2 agonist peptide (SLIGKV-NH 2 ). These findings suggest that AC-17 blocks radiographic contrast medium-induced pulmonary dysfunction by maintaining the endothelial barrier function. Thus, the compound is potentially useful for the prophylaxis of contrast media-induced acute pulmonary adverse events during angiography.

Flavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination between troxerutin 150 mg and carbazochrome 1.5 mg (Fleboside ampoules) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids. The purpose of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients. 30 patients were randomized to receive one of two treatments: troxerutin 150 mg and carbazochrome 1.5 mg, or placebo, i.m. 3 ml ampoules twice a day for five consecutive days after the surgical procedure, starting from the day of surgery. Efficacy parameters were assessed as follows: at baseline (T1), after the first administration (T2; day of surgery), the second day after the surgical procedure (T3), and the fifth day after the surgical procedure (T4); hemorrhoidal symptoms based on a visual analogue scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; analgesic intake, if any; time to restore a physiological defecation; edema evaluation (based on a four-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe); camera pictures taken at T1 and T4 (in selected patients); and blood coagulation tests. Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score (p = 0.007 and p = 0.001, respectively) in favor of the active combination treatment. A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 (p0.001) in favor of the active combination group. No adverse events were reported. Neither the active combination nor placebo affected blood coagulation tests. We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and carbazochrome 1.5 mg is effective, well tolerated and superior to placebo in improving hemorrhoidal and post-surgical symptoms during the five days following surgery.

Objective We report the case of a 47-year-old man with depression who developed acute dyspnea, hypoxemia, and mild hemoptysis after electroconvulsive therapy (ECT). Method Intravenous carbazochrome sodium sulfate hydrate as a hemostatic drug (100 mg/day) was prescribed for 2 days. On the day of ECT, oxygen inhalation (4 L/min) was continued, and SpO2 was maintained at 94–96%. Results Chest radiography showed improvement in alveolar infiltration. Chest CT 6 days after ECT also confirmed the disappearance of ground glass opacities in the lung fields. Conclusion(s) NPE is lifethreatening and should be recognized as an uncommon adverse event associated with ECT.

We evaluated the effects of drugs that included water extracts of Carthamus tinctorius L (E-C), β-glycyrrhetinic acid (Gly.), carbazochrome (Carz.), alone or in combination with (Mx.) and chlorhexidine (CHX) on the inflamed gingiva induced by accelerated plaque accumulation in Beagle dogs. After a clinically healthy gingiva was obtained by means of scaling and tooth brushing for 4 to 6 weeks, gingival inflammation was induced by the placement of silk floss ligatures around the premolars and molars and by feeding a soft diet for one week. The drugs were topically applied with a silicon gum tray for 5 and 10 days after inducement of gingivitis. A significant reduction of the number of infiltrated PMNs in the connective tissues adjacent to the upper part of the sulcular epithelium was observed with all drugs applied to gingiva at 10 days after the application. These findings suggested that E-C, Gly., Carz., as well as CHX are effective in the treatment of gingivitis singly or in combination.

Adrenochrome is one of the principal oxidation products of epinephrine and has no significant pressor action. It has been studied in Europe since 1937 and in America since 1951 for its action in control of bleeding from capillaries and venules. Its role seems independent of the chemistry of coagulation, the vitamin K-prothrombin mechanism, and the function of heparin or the usual anticoagulants. It is alleged to reduce capillary permeability and to increase capillary resistance,* a statement echoing data in regard to rutin several years ago. Both natural and synthetic adrenochrome are markedly unstable and insoluble. Evolution of the adrenochrome monosemicarbazone sodium salicylate complex has overcome these chemical difficulties. This product is synthetically prepared in America under the trade name Adrenosem and the generic name of carbazochrome. PREVIOUS REPORT In an uncontrolled, preliminary report of 69 private patients with bleeding problems, Sherber 4 found gratifying clinical courses following carbazochrome administration in

The hemostatic effect of Menaquinone-4 (K2) on bleeding at partially incised tail vein of rats pretreated with Dicumarol, Urokinase or Carbon Tetrachloride to prolong definitely bleeding time was studied. The effect of K2 on the bleeding was compared with the effects of Phytonadion (K1), Etamsylate, Tranexamic Acid (AMCHA), Epsilone Aminocaproic Acid (EACA) and Carbazochrome (CA-17). Intramuscularly administered K2, K1 and AMCHA showed statistically significant effect on shortening bleeding time on the rats given Dicumarol but K2 was the most potent. The bleeding time on K2-administered rats pretreated with Carbon Tetrachloride was significantly shortened, but K1 showed no effect. The bleeding time on the rats given Urokinase was apparently reduced by AMCHA, while K2 and K1 were not significantly effective.

Adrenochrome is an oxidation product of adrenaline (epinephrine) as shown by Green and Richter (1937). Both compounds are unstable, but Braconier et al. (1943) found that when adrenochrome is combined with monosemicarbazone the resulting compound adrenochrome monosemicarbazide (carbazochrome) is stable. This substance is poorly soluble but becomes much more soluble in the form of a sodium salicylate complex and can be given by intramuscular injection or orally. The official name for this compound is carbazochrome salicylate.

THE CONTROL of bleeding is a major surgical problem. This is particularly true in plastic surgery where oozing may endanger the success of a procedure and where bleeding points may be inaccessible. An operative field continuously deluged with blood makes precise, anatomic dissection difficult if not impossible. Excessive operative bleeding causes an increase not only in anesthesia time but in morbidity and mortality. Postoperative bleeding may compromise an otherwise good technical result in any operative procedure. The problem would be minimized if a systemic hemostatic agent could be administered preoperatively to the patient. Carbazochrome (Adrenosem) salicylate, one of the oxidation products of epinephrine, has been promoted as such an agent. There have been numerous reports of its success 1-13 and few reports of its failure. 14-16 The Council on Drugs of the American Medical Association has cautioned that there is insufficient evidence to prove that cessation of bleeding could