Summary Treatment of refractory cutaneous lupus is challenging. When conventional therapy, including hydroxychloroquine (HCQ), corticosteroids and immunosuppressants, has failed, the addition of quinacrine may be a promising option. We describe a case of refractory chronic cutaneous lupus erythematosus (CCLE) who responded well to quinacrine.
Quinacrine ; Lupus Erythematosus, Cutaneous

BACKGROUND: Profound anesthesia with adequate duration is required in periodontal flap surgery, which involves the manipulation of both hard and soft tissues. The anterior middle superior alveolar (AMSA) injection may be an alternative to multiple injections required for this purpose in the maxilla. The present study aimed to assess the effectiveness of AMSA injection using computer-controlled local anesthetic delivery (CCLAD) system to anesthetize buccal hard tissue (BHT), buccal soft tissue (BST), palatal hard tissue (PHT), and palatal soft tissue (PST) around the maxillary teeth. METHODS: Thirty-five patients who were indicated for open flap debridement in a whole maxillary quadrant were given AMSA injection using the CCLAD. The effectiveness of anesthesia was evaluated using subjective and objective parameters around each tooth. Supraperiosteal infiltrations were administered to complete the surgery wherever the AMSA injection was ineffective. RESULTS: The AMSA injection was more effective on the palatal tissues than on the buccal tissues, as 94.14% of PST and 87.89% of PHT sites were anesthetized compared to 49.22% and 43.75% of BHT and BST sites, respectively. There was no significant difference in the frequency of anesthesia around the anterior and posterior teeth. The PHT was significantly more anesthetized (P = 0.003) in males than in females. CONCLUSIONS: The AMSA injection using CCLAD is highly effective on palatal tissues and could be used as a first-line anesthesia for periodontal flap surgery. However, its effect on buccal tissues is less predictable, with supraperiosteal infiltration often required to supplement the AMSA injection.
Amsacrine ; Anesthesia ; Anesthetics, Local ; Butylated Hydroxytoluene ; Debridement ; Female ; Humans ; Male ; Maxilla ; Palate ; Periodontal Debridement ; Tooth

Periodontal procedures require adequate anesthesia not only to ensure the patient's comfort but also to enhance the operator's performance and minimize chair time. In the maxilla, anesthesia is often achieved using highly traumatic nerve blocks, apart from multiple local infiltrations through the buccal vestibule. In recent years, anterior middle superior alveolar (AMSA) field block has been claimed to be a less traumatic alternative to several of these conventional injections, and it has many other advantages. This critical review of the existing literature aimed to discuss the rationale, mechanism, effectiveness, extent, and duration of AMSA injections for periodontal surgical and non-surgical procedures in the maxilla. It also focused on future prospects, particularly in relation to computer-controlled local anesthetic delivery systems, which aim to achieve the goal of pain-free anesthesia. A literature search of different databases was performed to retrieve relevant articles related to AMSA injections. After analyzing the existing data, it can be concluded that this anesthetic technique may be used as a predictable method of effective palatal anesthesia with adequate duration for different periodontal procedures. It has additional advantages of being less traumatic, requiring lesser amounts of local anesthetics and vasoconstrictors, as well as achieving good hemostasis. However, its effect on the buccal periodontium appears highly unpredictable.
Amsacrine ; Anesthesia ; Anesthetics, Local ; Hemostasis ; Maxilla ; Methods ; Nerve Block ; Palate ; Periodontal Debridement ; Periodontium ; Vasoconstrictor Agents

OBJECTIVE: Nearly 20% of patients with critical limb ischemia will not be suitable for arterial bypass due to distal small vessel occlusion, and venous arterialization of the distal venous bed might be a valuable surgical option. This study demonstrates the in-vivo microcirculatory effects of this type of intervention.

METHODS: Using intravital video microscopy, the authors studied the distal skeletal microcirculatory characteristics following venous arterialization of critical hindlimb ischemia in the rat. 25 Wistar rats underwent proximal ligation of the femoral arteries followed by venous arterialization carried out by anastomosing the saphenous vein to the femoral artery using microsurgery techniques. Microcirculatory hemodynamic conditions of the soleus muscle were observed under normal, ischemic, and arterialized conditions. Fluorescein-labeled red cells were used to measure red cell velocities (Vrbc) at the capillaries, and acridine orange injections used to stain endothelial cell nuclei to measure microcirculatory diameters, and leukocyte nuclei to measure leukocyte adhesion. Laser Doppler Perfusion (LDP) units at the distal limb were measured continuously throughout the procedure.

RESULTS: Proximal femoral arterial ligation resulted in drastic reductions in LDP and Vrbc. Following distal venous arterialization, LDP returned to an average of 41% of baseline. Vrbc returned to near baseline values in 70% of the capillaries. Flow at the capillary and venular system showed frequent reversals and great variations in velocities. Venules and venu-venular anastomoses diameters increased by 50%. There was immediate macromolecular tracer leakage and leukocyte activation was significantly increased in both ischemic and arterialized groups (15 cells vs 156 and 178 cells respectively).

CONCLUSION: Venous arterialization may provide an improvement in microcirculatory velocities but is accompanied by microcirculatory injury and dysfunction in the acute phase. These results suggest that mechanisms besides microcirculatory hemodynamics play a role in the overall picture of clinical effectivity of the procedure

Animal ; Male ; Rats, Wistar ; Saphenous Vein ; Acridine Orange ; Venules ; Ischemia ; Femoral Vein ; Leukocytes ; Hemodynamics ; Muscle, Skeletal ; Hindlimb ; Endothelial Cells

BACKGROUND: Periodontitis is generally a chronic disorder characterized by the breakdown of tooth-supporting tissues. P. gingivalis, a Gram-negative anaerobic rod, is one of the major pathogens associated with periodontitis. Frequently, P. gingivalis infection leads to cell death. However, the correlation between P. gingivalis–induced cell death and periodontal inflammation remains to be elucidated. Among cell deaths, the death of immune cells appears to play a significant role in inflammatory response. Thus, the aim of this study was to examine P. gingivalis–induced cell death, focusing on autophagy and apoptosis in THP-1 cells. METHODS: Human acute monocytic leukemia cell line (THP-1) was used for all experiments. Autophagy induced by P. gingivalis in THP-1 cells was examined by Cyto ID staining. Intracellular autophagic vacuoles were observed by fluorescence microscopy using staining Acridine orange (AO); and 3-methyladenine (3-MA) was used to inhibit autophagy. Total cell death was measured by LDH assay. Cytokine production was measured by an ELISA method. RESULTS: P. gingivalis induced autophagy in an MOI-dependent manner in THP-1 cells, but 3-MA treatment decreased autophagy and increased the apoptotic blebs. P. gingivalis infection did not increase apoptosis compared to the control cells, whereas inhibition of autophagy by 3-MA significantly increased apoptosis in P. gingivalis-infected THP-1 cells. Inhibition of autophagy by 3-MA also increased total cell deaths and inflammatory cytokine production, including IL-1β and TNF-α. CONCLUSION: P. gingivalis induced autophagy in THP-1 cells, but the inhibition of autophagy by 3-MA stimulated apoptosis, leading to increased cell deaths and pro-inflammatory cytokines production. Hence, the modulation of cell deaths may provide a mechanism to fight against invading microorganisms in host cells and could be a promising way to control inflammation.
Acridine Orange ; Apoptosis ; Autophagy ; Blister ; Cell Death* ; Cell Line ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Leukemia, Monocytic, Acute ; Macrophages ; Methods ; Microscopy, Fluorescence ; Periodontitis ; Porphyromonas gingivalis* ; Porphyromonas* ; Vacuoles

BACKGROUND AND OBJECTIVES: Dilated cardiomyopathy can be the end-stage of severe cardiac disorders and directly affects the cardiac muscle, inducing cardiomegaly and heart failure (HF). Although a wide variety of animal models are available to study dilated cardiomyopathy, there is no model to assess dilated cardiomyopathy with non-invasive, simple, and large screening methods. METHODS: We developed a dilated cardiomyopathy model in zebrafish larvae using short duration terfenadine, a known cardiotoxic drug that induces ventricular size dilation. Fractional shortening of zebrafish hearts was calculated. RESULTS: We treated zebrafish with 5 to 10 µM terfenadine for 24 hours. In terfenadine-treated zebrafish, blood frequently pooled and clotted in the chamber, and circulation was remarkably reduced. Atria and ventricles were swollen, and fluid was deposited around the heart, mimicking edema. Cardiac contractility was significantly reduced, and ventricular area was significantly enlarged. Heart rate was markedly reduced even after terfenadine withdrawal. Acridine orange staining also showed that terfenadine increased cardiomyocyte apoptosis. A significant increase of natriuretic peptide B (NPPB) mRNA was found in terfenadine-treated zebrafish. A low dose of terfenadine (5–10 µM) did not show mortality in short-term treatment (24 hours). However, moderate dose (35–45 µM) terfenadine treatment reduced zebrafish survival within 1 hour. CONCLUSION: With advantages of rapid sample preparation procedure and transparent observation of the live heart, this model can potentially be applied to large-scale drug screening and toxicity assays for non-ischemic HF.
Acridine Orange ; Apoptosis ; Cardiomegaly ; Cardiomyopathies ; Cardiomyopathy, Dilated* ; Drug Evaluation, Preclinical ; Edema ; Heart ; Heart Failure ; Heart Rate ; Larva* ; Mass Screening ; Models, Animal ; Mortality ; Myocardium ; Myocytes, Cardiac ; RNA, Messenger ; Terfenadine* ; Zebrafish*

We investigated the role of autophagy in SNUC5/5-FUR, 5-fluorouracil (5-FU) resistant SNUC5 colon cancer cells. SNUC5/5-FUR cells exhibited low level of autophagy, as determined by light microscopy, confocal microscopy, and flow cytometry following acridine orange staining, and the decreased level of GFP-LC3 puncta. In addition, expression of critical autophagic proteins such as Atg5, Beclin-1 and LC3-II and autophagic flux was diminished in SNUC5/5-FUR cells. Whereas production of reactive oxygen species (ROS) was significantly elevated in SNUC5/5-FUR cells, treatment with the ROS inhibitor N-acetyl cysteine further reduced the level of autophagy. Taken together, these results indicate that decreased autophagy is linked to 5-FU resistance in SNUC5 colon cancer cells.
Acridine Orange ; Autophagy* ; Colon* ; Colonic Neoplasms* ; Cysteine ; Flow Cytometry ; Fluorouracil* ; Microscopy ; Microscopy, Confocal ; Reactive Oxygen Species

Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of –5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of –7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.
Amodiaquine ; Berberine ; Brazil ; Catalytic Domain ; Congenital Abnormalities ; Culicidae ; Dengue Virus ; Drug Design ; Flaviviridae ; Flavivirus ; Genome ; High-Throughput Screening Assays ; Humans ; Mass Screening* ; Microcephaly ; Molecular Docking Simulation ; Pregnancy ; Prochlorperazine ; Quinacrine ; RNA ; United States Food and Drug Administration ; Zika Virus* ; Zinc

OBJECTIVE: Diabetes mellitus (DM) is known to cause many systemic complications as well as male infertility. Astaxanthin (ASTX) is a powerful antioxidant that is involved in a variety of biologically active processes, including those with anti-diabetes effects. The present study investigates the effect of ASTX on the spermatozoa function in streptozotocin (STZ)-induced diabetic rats. METHODS: We divided 30 adult rats into three groups (10 rats per group), with a control group that received corn oil mixed with chow. DM was induced by intra-peritoneal injection of STZ. Eight weeks after the STZ injection, half of the diabetic animals were used as diabetic controls, and the rest were treated with ASTX for 56 days. Then the parameters and chromatin integrity of the epididymal sperm were analyzed using chromomycin A3, toluidine blue (TB), and acridine orange (AO) staining. RESULTS: The count, viability, and motility of the epididymal sperm were decreased significantly in the STZ group in comparison with the control group (count and viability, p<0.001; motility, p<0.001;0.01). ASTX increased normal morphology and viable spermatozoa compared to the STZ group (morphology, p=0.001; viability, p<0.001;0.05). The percentage of abnormal chromatins in TB and AO staining was higher in the STZ group compared to the control group (p<0.001;0.001). The mean percentage of TB and AO positive spermatozoa in STZ rats was significantly lower in the STZ+ASTX group (TB, p=0.001; AO, p<0.001;0.05). CONCLUSION: This study observed that in vivo ASTX treatment partially attenuates some detrimental effect of diabetes. Conversely, ASTX improved sperm viability, normal morphology, and DNA integrity.
Acridine Orange ; Adult ; Animals ; Chromatin ; Chromomycin A3 ; Corn Oil ; Diabetes Mellitus ; Dietary Supplements* ; DNA* ; Humans ; Infertility, Male ; Male ; Rats* ; Spermatozoa* ; Streptozocin ; Tolonium Chloride

Severe liver dysfunction in pregnancy (SLDP) is rare but serious complications with high mortality rate. This study compared the effectiveness and safety of double-balloon catheter versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy in patients with SLD. A total of 55 patients with indications of labor induction were enrolled and analyzed by retrospective control analysis method. Twenty-three cases adopted Cook double balloon dilation as Cook group, and 32 cases received intra-amniotic injection of ethacridine lactate as EL group. The primary outcome was evaluated by successful abortion rate and the difference in the induction-to-abortion interval. Secondary outcomes included liver function recovery and the frequency of adverse events. Both Cook and EL regimens were effective, with successful abortion rate of 87.0% and 93.8%, respectively (P=0.639). The induction-to-delivery interval was similar between Cook group and EL group (38.1 ± 21.5 vs. 41.3 ± 17.4, P=0.543). The liver disease status was more severe in Cook group than in EL group, but it did not show any significant difference after pregnancy termination between the two groups and the improvement rate also did not show any significant difference. Both treatments were safe and there was no significant difference in bleeding and cervical laceration adverse events between the two groups. Our study firstly compared double-balloon catheter and ethacridine lactate for the induction of labor in women with SLD during second trimester pregnancy.
Abortion, Induced ; Catheters ; Ethacridine ; administration & dosage ; Female ; Humans ; Liver Diseases ; physiopathology ; Pregnancy ; Pregnancy Trimester, Second