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1.
Eur J Pharmacol ; 902: 174110, 2021 Jul 05.
Article En | MEDLINE | ID: mdl-33901457

There is an almost unlimited interest in searching and developing new drugs, especially when we are in an era that are witnessing more and more emerging pathogens. Natural products from traditional medicines represent a large library for searching lead compounds with novel bioactivities. Sodium houttuyfonate is such one bioactive compound derived from Houttuynia cordata Thunb which has been employed in traditional medicine for treating infectious and inflammatory diseases. Sodium houttuyfonate has demonstrated multiple kinds of pharmacological effects, including antifungal, antibacterial, anti-inflammatory, and cardiovascular protective activities, which are discussed here to provide insights into our understanding of the pharmacological effects of SH and the underlying mechanisms.


Alkanes/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antifungal Agents/pharmacology , Cardiotonic Agents/pharmacology , Sulfites/pharmacology , Alkanes/adverse effects , Alkanes/chemistry , Alkanes/therapeutic use , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Antifungal Agents/adverse effects , Antifungal Agents/chemistry , Antifungal Agents/therapeutic use , Cardiotonic Agents/adverse effects , Cardiotonic Agents/chemistry , Cardiotonic Agents/therapeutic use , Houttuynia/chemistry , Humans , Sulfites/adverse effects , Sulfites/chemistry , Sulfites/therapeutic use
2.
Respir Physiol Neurobiol ; 259: 75-85, 2019 01.
Article En | MEDLINE | ID: mdl-30086385

The role of cystathionine-γ-lyase (CSE) derived H2S in the hypoxic and anoxic responses of the carotid body (CB) were examined. Experiments were performed on Sprague-Dawley rats, wild type and CSE knockout mice on C57BL/6 J background. Hypoxia (pO2 = 37 ± 3 mmHg) increased the CB sensory nerve activity and elevated H2S levels in rats. In contrast, anoxia (pO2 = 5 ± 4 mmHg) produced only a modest CB sensory excitation with no change in H2S levels. DL-propargylglycine (DL-PAG), a blocker of CSE, inhibited hypoxia but not anoxia-evoked CB sensory excitation and [Ca2+]i elevation of glomus cells. The inhibitory effects of DL-PAG on hypoxia were seen: a) when it is dissolved in saline but not in dimethyl sulfoxide (DMSO), and b) in glomus cells cultured for18 h but not in cells either soon after isolation or after prolonged culturing (72 h) requiring 1-3 h of incubation. On the other hand, anoxia-induced [Ca2+]i responses of glomus cell were blocked by high concentration of DL-PAG (300µM) either alone or in combination with aminooxyacetic acid (AOAA; 300µM) with a decreased cell viability. Anoxia produced a weak CB sensory excitation and robust [Ca2+]i elevation in glomus cells of both wild-type and CSE null mice. As compared to wild-type, CSE null mice exhibited impaired CB chemo reflex as evidenced by attenuated efferent phrenic nerve responses to brief hyperoxia (Dejours test), and hypoxia. Inhalation of 100% N2 (anoxia) depressed breathing in both CSE null and wild-type mice. These observations demonstrate that a) hypoxia and anoxia are not analogous stimuli for studying CB physiology and b) CSE-derived H2S contributes to CB response to hypoxia but not to that of anoxia.


Carotid Body/drug effects , Cystathionine gamma-Lyase/metabolism , Hypoxia/pathology , Sulfites/therapeutic use , Action Potentials/drug effects , Animals , Calcium/metabolism , Carotid Body/pathology , Cells, Cultured , Cystathionine gamma-Lyase/genetics , Hypoxia/drug therapy , Male , Phrenic Nerve/drug effects , Phrenic Nerve/physiology , Rats , Rats, Sprague-Dawley , Sulfites/pharmacology
3.
Neurotox Res ; 34(1): 1-15, 2018 07.
Article En | MEDLINE | ID: mdl-29188487

How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment. It was found that voltage-gated Na+ current (I Na) was stimulated, and current inactivation and deactivation were slowed in SMB-treated (30 µM) HL-1 cardiomyocytes. SMB-induced increases of I Na were attenuated in cells treated with ranolazine (10 µM) or eugenol (30 µM). The current-voltage relationship of I Na shifted to slightly more negative potentials in SMB-treated cells, the peak I Na with an EC50 value of 18 µM increased, and the steady-state inactivation curve of I Na shifted to a more positive potential. However, the tail component of the rapidly activating delayed-rectifier K+ current (I Kr) was dose-dependently inhibited. Cell-attached voltage-clamp recordings in SMB-treated cells showed that the frequency of action currents and prolonged action potential were higher. In SMB-treated NSC-34 neurons, the peak I Na was higher; however, neither the time to peak nor the inactivation time constant (I Na) changed. Pilocarpine-induced seizures were exacerbated, and acute neuronal damage and chronic mossy fiber sprouting increased in SMB-treated rats. Western blotting showed higher expression of the sodium channel in cells after chronic SMB treatment. We conclude that SMB contributes to the sodium channel-activating mechanism through which it alters cellular excitability and excitotoxicity in wide-spectrum excitable cells.


Bronchoconstrictor Agents/pharmacology , Ion Channels/drug effects , Membrane Potentials/drug effects , Seizures/drug therapy , Sulfites/pharmacology , Alopecia/chemically induced , Animals , Biophysics , Body Weight/drug effects , Bronchoconstrictor Agents/therapeutic use , Cell Line, Transformed , Disease Models, Animal , Dose-Response Relationship, Drug , Electric Stimulation , Gene Expression/drug effects , Ion Channels/physiology , Male , Mice , Muscarinic Agonists/toxicity , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , NAV1.1 Voltage-Gated Sodium Channel/genetics , NAV1.1 Voltage-Gated Sodium Channel/metabolism , Neurons/drug effects , Neurons/physiology , Pilocarpine/toxicity , Rats , Rats, Sprague-Dawley , Seizures/chemically induced , Seizures/pathology , Skin/drug effects , Skin/pathology , Sulfites/therapeutic use
5.
Life Sci ; 143: 27-34, 2015 Dec 15.
Article En | MEDLINE | ID: mdl-26506573

AIM: The aim of this study is to determine the anticancer effect of sulfite on SH-SY5Y neuroblastoma cells in vitro conditions and elucidate underlying molecular mechanism of sulfite and explore its therapeutic activity. MAIN METHODS: In this study, cytotoxic effects of sulfite in SH-SY5Y cels were detected over time in a dose dependent manner with the IC50 doses ranging from 0.5 to 10 mM. Genotoxic effect of sulfite was shown by comet assay. IC50 doses in the SH-SY5Y cells were detected as 5 mM. Expression profiles of the target genes related to apoptosis and cell cycle control were determined by quantitative RT-PCR. Protein changes were determined by western blot analysis. KEY FINDINGS: URG4/URGCP, CCND1, CCND2, CDK4, CDK6, E2F4 and BCL-2 gene expression levels were significantly reduced and RB1, TP53, BAX, BID, CASP2, CASP3, CASP9 and DIABLO gene expressions were significantly increased in dose group cells. The mechanism of this result may be related to sulfite dependent inhibition of cell cycle at the G1 phase by down-regulating URG4/URGCP or CCND1, CDK4, CDK6 gene expression and stimulating apoptosis via the intrinsic pathway. Sulfite suppressed invasion and colony formation in SH-SY5Y cell line using matrigel invasion chamber and colony formation assay, respectively. SIGNIFICANCE: It is thought that sulfite demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis s, invasion, and colony formation on SH-SY5Y cells. Sulfite may be an effective agent for treatment of neuroblastoma as a single agent or in combination with other agents.


Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/biosynthesis , Neuroblastoma/metabolism , Oncogenes/drug effects , Sulfites/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Humans , Neuroblastoma/drug therapy , Oncogenes/physiology , Sulfites/therapeutic use , Treatment Outcome
6.
Braz J Med Biol Res ; 48(7): 622-8, 2015 Jul.
Article En | MEDLINE | ID: mdl-25945746

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.


Acute Kidney Injury/prevention & control , Drainage/methods , Gasotransmitters/therapeutic use , Hydrogen Sulfide/therapeutic use , Lymph/physiology , Shock, Hemorrhagic/therapy , Acute Kidney Injury/physiopathology , Alkynes/therapeutic use , Animals , Creatinine/blood , Cystathionine gamma-Lyase/analysis , Cytokines/analysis , Enzyme Inhibitors/therapeutic use , Enzyme-Linked Immunosorbent Assay , Gasotransmitters/analysis , Glycine/analogs & derivatives , Glycine/therapeutic use , Hydrogen Sulfide/analysis , Male , Mesentery , Rats, Wistar , Reproducibility of Results , Shock, Hemorrhagic/complications , Sulfites/therapeutic use , Time Factors , Treatment Outcome , Urea/blood
7.
Neurosurg Focus ; 37(6): E4, 2014 Dec.
Article En | MEDLINE | ID: mdl-25434389

OBJECT: The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol. METHODS: A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered. RESULTS: All patients but 1 in Group A survived at least 18 months (range 18-101 months), and patients in Group B survived no more than 17 months (range 2-17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group. CONCLUSIONS: This study describes the longest experience so far reported with TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, who were treated using GTR. Statistically significant data confirm that median survival correlates with MGMT promoter methylation status as well as with the number of TMZ cycles administered. Long-term TMZ therapy appears feasible and safe.


Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/drug therapy , Dacarbazine/analogs & derivatives , Glioblastoma/drug therapy , Adrenal Cortex Hormones/therapeutic use , Aged , Aged, 80 and over , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , DNA Methylation , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Dacarbazine/therapeutic use , Disease-Free Survival , Female , Glioblastoma/diagnosis , Glioblastoma/genetics , Humans , Karnofsky Performance Status , Ki-67 Antigen/metabolism , Longitudinal Studies , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Sulfites/therapeutic use , Temozolomide , Time Factors , Tumor Suppressor Proteins/genetics
8.
Dent Mater J ; 31(5): 797-805, 2012.
Article En | MEDLINE | ID: mdl-23037843

It is attempted to augment a coating resin with a bleaching effect to provide both short- and long-term whitening effects. Base resin containing sodium percarbonate (SPC) effectively bleached bovine teeth discolored by the Maillard reaction. SPC did not reduce Vickers hardness, but hardness in the hybrid material increased. The shear bonding strength of SPC-containing resin was low. No inflammation was apparent in hamster cheek pouch mucosa when exposed to SPC resin covered with a layer of base resin. H(2)O(2) was released into buffer from this resin, but when placed onto tooth tissue with a protective layer of base resin, penetration of H(2)O(2) into the pulp chamber was undetectable. It is concluded that SPC resin equipped with a bleaching aid can be safely used as a coating material for discolored teeth.


Coated Materials, Biocompatible/chemistry , Tooth Bleaching Agents/therapeutic use , Tooth Discoloration/drug therapy , Animals , Benzoyl Peroxide/therapeutic use , Bisphenol A-Glycidyl Methacrylate/chemistry , Borates/therapeutic use , Carbamide Peroxide , Carbonates/chemistry , Cattle , Color , Colorimetry , Cricetinae , Dental Bonding , Dental Enamel/drug effects , Dental Pulp/drug effects , Drug Carriers , Hardness , Hydrogen Peroxide/chemistry , Light-Curing of Dental Adhesives , Male , Mesocricetus , Mouth Mucosa/drug effects , Peroxides/therapeutic use , Polymethacrylic Acids/chemistry , Shear Strength , Stress, Mechanical , Sulfites/therapeutic use , Tooth Bleaching/methods , Tooth Bleaching Agents/chemistry , Urea/analogs & derivatives , Urea/therapeutic use
9.
J Ethnopharmacol ; 131(1): 203-9, 2010 Aug 19.
Article En | MEDLINE | ID: mdl-20600768

AIMS OF THE STUDY: Sodium houttuyfonate (SH) is an addition compound of sodium bisulfite and houttuynin. Houttuynin is one of the main ingredients in the volatile oil of Houttuynia cordata Thunb, which has been widely used in traditional Chinese medicines. In this study, we investigated the effect of SH in membranous glomerulonephritis (MGN) induced by cationic Bovine Serum Albumin (C-BSA) in BALB/c mice. MATERIALS AND METHODS: Mice were divided into four groups, including normal vehicle-treated controls (N group), model (M group), low SH of 60 mg/kg body weight (L group), or high SH of 120 mg/kg body weight (H group). Urine protein quantification was detected by the urine protein strip test. Morphological assessment in kidneys was observed by light microscope and electron microscopy. The level of nuclear factor-kappaB (NF-kappaB) in the nuclear was evaluated by Western blot. Immunohistochemical was used to analyze the expression of MCP-1. RESULTS: SH was shown to reverse C-BSA induced increases in urinary protein, and changes in morphology. Treatment with SH at 60-120 mg/kg (L and H groups, respectively) dose-dependently decreased the level of nuclear NF-kappaB and MCP-1 expression compared to that of the M group. CONCLUSIONS: This study reveals that SH could treat C-BSA induced MGN in BALB/c mice by suppressing NF-kappaB activation and MCP-1 expression. Therefore, the most likely mechanism underlying the biological effects of SH is inhibition of an NF-kappaB mediated-cytokine pathway.


Alkanes/pharmacology , Alkanes/therapeutic use , Chemokine CCL2/biosynthesis , Gene Expression Regulation/drug effects , Glomerulonephritis, Membranous/metabolism , NF-kappa B/biosynthesis , Sulfites/pharmacology , Sulfites/therapeutic use , Animals , Cattle , Chemokine CCL2/antagonists & inhibitors , Chemokine CCL2/genetics , Female , Glomerulonephritis, Membranous/drug therapy , Glomerulonephritis, Membranous/pathology , Male , Mice , Mice, Inbred BALB C , NF-kappa B/antagonists & inhibitors
10.
J Neurooncol ; 97(1): 33-40, 2010 Mar.
Article En | MEDLINE | ID: mdl-19705067

Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5'-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma.


Brain Neoplasms/mortality , Glioma/mortality , Intracellular Signaling Peptides and Proteins/metabolism , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/physiology , Adult , Brain Neoplasms/drug therapy , Female , Gene Expression Regulation, Neoplastic/drug effects , Glioma/drug therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Phosphorylation/drug effects , Predictive Value of Tests , Retrospective Studies , Serine/metabolism , Signal Transduction/drug effects , Statistics, Nonparametric , Sulfites/pharmacology , Sulfites/therapeutic use , TOR Serine-Threonine Kinases , Young Adult
11.
J Clin Periodontol ; 35(7): 614-20, 2008 Jul.
Article En | MEDLINE | ID: mdl-18422695

UNLABELLED: The use of chlorhexidine (CHX) has been recommended for a number of clinical applications including plaque control in the post-operative period. However, the use of CHX is burdened by some side effects that could affect the compliance of the patient. The aim of this clinical trial was to evaluate the side effects, the staining in particular, the patient acceptance, and the efficacy of a 0.2% CHX mouthwash containing an anti discoloration system (ADS) compared with a 0.2% CHX alone, after periodontal flap surgery. MATERIAL AND METHODS: This single-centre, cross-over, triple-blind randomized clinical trial was carried out on 48 consecutive patients. After periodontal flap surgery, the patients were prescribed to rinse two times per day for 1 min for 1 week with 10 ml of test or control CHX, contained in anonymous bottles coded K or M and assigned randomly. No brushing and interdental cleaning of the surgical area was allowed. At week 1, after suture removal, patients received full-mouth prophylaxis and were given a second anonymous bottle, reversing the products, with the same instructions as at baseline. Patients resumed tooth-brushing but not interdental cleaning. At the end of week 2, prophylaxis was repeated, mouth rinsing was discontinued and patients resumed normal oral hygiene. At weeks 1 and 2, the following variables were recorded: presence of pigmentation, gingival parameters at the surgically treated sites (gingival inflammation, tissue inflammation around the sutures, gingival swelling and presence of granulation tissue), patient perception and acceptance of the 2 mouthwashes. RESULTS: Forty-seven patients completed the study. The difference between treatments related to gingival variables was not statistically significant. The test CHX caused consistently less pigmentations than the control CHX in all the evaluated areas of the dental surfaces (odds ratio (OR)=0.083 p<0.0001 in the incisal area, OR=0.036 p<0.0001 in the approximal area and OR=0.065 p<0.0001 in the gingival area). The CHX ADS was found to be more tolerated by patients than the control mouthwash and to cause less food alteration, less alterations to the perception of salt and to be less irritant for the oral tissues. CONCLUSIONS: (1) CHX ADS caused less pigmentation, was burdened by less side effects and was more agreeable than the control CHX; (2) CHX ADS was as effective as CHX without ADS in reducing gingival signs of inflammation in the post-surgical early healing phase; (3) the use of CHX ADS could be of value in treatment protocols in which the patient compliance with a CHX mouthwash prescription is relevant.


Chlorhexidine/therapeutic use , Gingiva/drug effects , Mouthwashes/therapeutic use , Periodontitis/surgery , Tooth Discoloration/prevention & control , Adult , Aged , Anti-Infective Agents, Local/adverse effects , Anti-Infective Agents, Local/therapeutic use , Ascorbic Acid/therapeutic use , Chlorhexidine/adverse effects , Cross-Over Studies , Dental Plaque/prevention & control , Double-Blind Method , Female , Humans , Linear Models , Male , Middle Aged , Mouthwashes/adverse effects , Mouthwashes/chemistry , Patient Compliance , Sulfites/therapeutic use , Surgical Flaps , Taste/drug effects , Tooth Discoloration/chemically induced , Treatment Outcome , Wound Healing/drug effects
12.
Eur J Anaesthesiol ; 23(4): 341-5, 2006 Apr.
Article En | MEDLINE | ID: mdl-16438763

BACKGROUND AND OBJECTIVE: We compared the dose requirement and side effect profile of total intravenous anaesthesia using Diprivan to generic propofol at a specific anaesthetic target level utilizing the bispectral index monitor to determine efficacy differences between the two products. METHODS: Sixty women undergoing abdominal hysterectomy were induced with propofol 2 mg kg-1 and maintained with infusion (20-200 microg kg-1 min-1) adjusted to maintain a bispectral index of 50-65. Plasma propofol concentration was measured at 1 and 2 h post induction in 25 patients. RESULTS: Mean (SD) drug doses adjusted for weight and time were similar in the Diprivan and generic propofol groups: 90 (30) microg kg-1 min-1 vs. 90 (20) microg kg-1 min-1 respectively. Mean (SD) plasma propofol levels at 1 and 2 h were also similar (3.0 (1.0) microg mL-1 vs. 3.6 (1.4) microg mL-1, P = 0.2 and 3.0 (1.9) microg mL-1 vs. 3.4 (1.6) microg mL-1, P = 0.58). CONCLUSIONS: Diprivan and generic propofol have similar efficacy at a specified, bispectral index-defined, depth of anaesthesia.


Drugs, Generic/therapeutic use , Propofol/therapeutic use , Sulfites/therapeutic use , Adult , Double-Blind Method , Drugs, Generic/pharmacology , Electroencephalography/drug effects , Female , Humans , Hysterectomy , Middle Aged , Propofol/pharmacology , Prospective Studies , Sulfites/pharmacology
13.
Int J Dent Hyg ; 2(3): 122-6, 2004 Aug.
Article En | MEDLINE | ID: mdl-16451475

UNLABELLED: Correct oral hygiene is believed to be the basis of primary and secondary prevention. Sometimes, using a toothbrush or other mechanical instruments for oral hygiene may be difficult and it may become necessary to use an antiseptic. Chlorhexidine is an essential component in many available preparations on sale, because of its marked antiseptic qualities. One of the most frequent side-effects is the appearance of stains on the teeth and mucous membranes, which particularly disturbs the patient. A new mouthwash containing chlorhexidine has recently become available, besides maintaining its antiseptic qualities, also avoids the side-effect of staining. OBJECTIVES: The aim of this study was to check the capacity of the new mouthwash, which contains chlorhexidine and Anti Discoloration System (ADS), not only to prevent plaque formation like the other mouthwashes containing chlorhexidine but also to avoid staining that is one of the most frequent side-effects. STUDY DESIGN: The comparative study was carried out on a sample of 15 patients treated with two mouthwashes both containing 0.2% chlorhexidine, but different in that the first does not contain ADS, which is instead present in the second, a new product. The results obtained show that in the 15 patients treated, there is no statistically significant difference in the ability of the mouthwash to prevent bacterial plaque, however evidence of the stain was much less with the new mouthwash.


Anti-Infective Agents, Local/adverse effects , Chlorhexidine/adverse effects , Mouthwashes/adverse effects , Tooth Discoloration/prevention & control , Adult , Ascorbic Acid/therapeutic use , Chemistry, Pharmaceutical , Colorimetry , Dental Plaque/prevention & control , Dental Plaque Index , Female , Free Radical Scavengers/therapeutic use , Humans , Male , Middle Aged , Mouthwashes/chemistry , Periodontal Index , Pharmaceutic Aids/therapeutic use , Single-Blind Method , Sulfites/therapeutic use , Tooth/drug effects , Tooth/pathology , Tooth Cervix/drug effects , Tooth Cervix/pathology , Tooth Discoloration/chemically induced
14.
Acta Paediatr ; 90(12): 1405-10, 2001 Dec.
Article En | MEDLINE | ID: mdl-11853338

UNLABELLED: In preliminary observations, significant amounts of free cysteine, a neurotoxic amino acid, were noted in the urine of asphyxiated or septic-shocked neonates. The present study was conducted to determine whether free urinary cysteine was elevated in these critically ill neonates compared with a control group, and to assess the clinical significance of this generation. Free cysteine was measured in the urine of newborn infants with perinatal asphyxia (n = 16) or neonatal sepsis (n = 14) and the urine of a control group (n = 10) by ion-exchange chromatography. Relationships between cysteine levels and the clinical severity, sulfite supply and neurological outcome of the patients were then studied. Urinary cysteine was 27.6 (15-49) mmol mol(-1) creatinine for the patients but was not detectable in the control group. Cysteine levels were correlated with the severity of neonatal septic shock but not with the grade of perinatal asphyxia and did not have a specific influence on the neurological outcome of these patients. The correlation between cysteine level and the severity of neonatal septic shock was indirect and probably linked to higher sulfite administration in this population. CONCLUSION: The mean daily supply of sulfites is high in critically ill neonates, mainly originating from dopamine and generating significant amounts of cysteine. Although a worsening effect attributable to cysteine on the neurological outcome of the patients could not be demonstrated, the appropriateness of cryptic administration of sulfites by way of drug excipients is called into question.


Asphyxia Neonatorum/complications , Asphyxia Neonatorum/urine , Critical Illness , Cysteine/urine , Nervous System Diseases/etiology , Outcome Assessment, Health Care , Shock, Septic/complications , Shock, Septic/urine , Apgar Score , Asphyxia Neonatorum/drug therapy , Gestational Age , Humans , Infant, Newborn , Nervous System Diseases/urine , Severity of Illness Index , Shock, Septic/drug therapy , Sulfites/adverse effects , Sulfites/therapeutic use
15.
Neurogenetics ; 2(3): 183-8, 1999 Sep.
Article En | MEDLINE | ID: mdl-10541593

Familial amyloidotic polyneuropathy (FAP) and senile systemic amyloidosis (SSA) are characterized by systemic extracellular deposition of insoluble transthyretin (TTR) fibrils. While only normal TTR is found in fibrils from SSA patients who predominantly suffer from cardiomyopathy, autosomal dominant FAP preferentially affects peripheral nerves and heart and is associated with so-called amyloidogenic mutations of this protein, giving rise to TTR forms of decreased stability. Using isoelectric focusing in urea gradients we were able to demonstrate a stabilizing effect of sulfite on TTR monomers and tetramers, as well as an increase in the tetramer/monomer ratio. We demonstrate that this ratio, which is decreased in FAP patients, can be increased to beyond normal levels. We show that doses of sulfite which are tolerable in vivo produce a significant increase in the tetramer/monomer ratio and postulate that sulfite may be a potent drug for delaying the onset and progress of FAP and SSA.


Amyloid Neuropathies/drug therapy , Amyloid Neuropathies/genetics , Prealbumin/genetics , Sulfites/therapeutic use , Amyloid Neuropathies/pathology , Humans , Ligands , Point Mutation , Prealbumin/chemistry , Prealbumin/metabolism , Protein Binding/genetics , Protein Conformation , Sulfites/metabolism , Titrimetry , Urea/analysis , Urea/blood
16.
Food Addit Contam ; 15(2): 171-80, 1998.
Article En | MEDLINE | ID: mdl-9602923

Studies were performed on the efficacy, residues and in vitro enterocyte toxicity of 4-hexylresorcinol (4-HR), which could be utilized as an inhibitor of shrimp melanosis (black spot). Mediterranean sea shrimp (Parapaeneus longirostris) were treated with solutions of 4-HR in sea-water, at three different concentrations, 25, 50 or 100 mg/kg of shrimp, to test its antioxidative property. As a comparison a group of shrimp was treated with sodium metabisulphite (1 g/kg), while another group was left untreated. 4-HR showed a marked ability to inhibit or slow down melanosis (black spot) in shrimp; the most effective concentration was 100 mg/kg within an optimum period of 7 days but with effects up to the tenth day. During the first 5 days, 4-HR residues in the edible part of the shrimp showed a fast decrease in all three groups, going from initial average values of 20 mg/kg at 0 time, to 0.9 in the group treated at 25 mg/kg; from 42 to 1.8 mg/kg in the group at 50 mg/kg and from 85 to 1.9 mg/kg in the group at 100 mg/kg. In vitro studies on enterocyte-like Caco-2 cells did not indicate any cytotoxic effect up to a concentration of 50 micrograms/ml. Moreover, no inhibition of protein synthesis was observed, which lends further support to the absence of significant damage to the intestinal mucosa induced by 4-HR. The available database on 4-HR pharmacology and toxicology is inadequate to determine even a provisional ADI. There is negative evidence of carcinogenesis and no significant untoward effects were observed in humans when it was used as an anthelmintic. However, it is not possible to determine a NOEL for non-genotoxic effects. 4-HR could become an interesting alternative to the use of sulphites to prevent black spot. However, a more complete database is needed to achieve a regulatory evaluation.


Caco-2 Cells/drug effects , Decapoda , Hexylresorcinol/therapeutic use , Melanosis/veterinary , Animals , Cell Survival/drug effects , Decapoda/chemistry , Hexylresorcinol/adverse effects , Humans , Melanosis/prevention & control , Sulfites/therapeutic use
17.
Am J Contact Dermat ; 9(1): 11-4, 1998 Mar.
Article En | MEDLINE | ID: mdl-9471981

BACKGROUND: Skin exposure to biocides containing high concentrations of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) may cause both severe chemical burns and induce sensitization. OBJECTIVE: This study was performed to investigate whether sodium bisulfite, as a model substance, could be used for treatment of skin accidentally exposed to high concentrations of MCI/MI to prevent chemical burns and elicitation of allergic contact dermatitis. METHODS: The reaction between Kathon WT and sodium bisulfite was studied with chemical methods. MCI/MI-hypersensitive patients and controls were patch tested with serial dilutions of Kathon CG and with reaction mixtures being about 30 seconds, 30 minutes, and 48 hours old. RESULTS: The concentrations of MCI/MI rapidly decreased after addition of sodium bisulfite. The degradation products did not elicit any irritant test reactions neither in test patients nor in controls. Five out of seven Kathon CG-hypersensitive patients reacted to a reaction mixture about 30 seconds old and containing MCI/MI at 14 ppm, whereas four and two individuals tested positively to the reaction mixtures being 30 minutes and 48 hours old, respectively. The controls tested negatively to all reaction mixtures. All tested persons reacted negatively to sodium bisulfite. CONCLUSIONS: The deactivation of MCI/MI with sodium bisulfite occurred instantly and it prevented corrosive skin reactions and the elicitation of allergic contact dermatitis was decreased substantially.


Burns, Chemical/prevention & control , Dermatitis, Allergic Contact/prevention & control , Sulfites/therapeutic use , Thiazoles/adverse effects , Burns, Chemical/etiology , Chromatography, High Pressure Liquid , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Disinfectants/adverse effects , Humans , Patch Tests , Sulfites/administration & dosage
18.
J Korean Med Sci ; 11(4): 356-7, 1996 Aug.
Article En | MEDLINE | ID: mdl-8878807

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms.


Allergens/therapeutic use , Edema/etiology , Orbital Diseases/etiology , Sulfites/therapeutic use , Female , Humans , Middle Aged , Skin Diseases/drug therapy
19.
Article En | WPRIM | ID: wpr-192894

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms.


Female , Humans , Allergens/therapeutic use , Edema/etiology , Middle Aged , Orbital Diseases/etiology , Skin Diseases/drug therapy , Sulfites/therapeutic use
20.
Ann Allergy ; 71(6): 563-6, 1993 Dec.
Article En | MEDLINE | ID: mdl-8267251

Since the introduction of sodium metabisulfite as a food preservative, it has been associated with several idiosyncratic reactions (eg, bronchospasm, oculonasal symptoms, and urticaria/angioedema) in sulfite-sensitive individuals. The pathogenic mechanism of these reactions is not yet understood. We report the case of two crewmen on a shrimp trawler who were found dead in the ship's hold. Their deaths had occurred while they were applying dry sodium metabisulfite, referred to as "shrimp dip" in the shrimping industry. Postmortem examinations showed diffuse pulmonary edema consistent with death secondary to asphyxia. Associated findings were visceral congestion. Although it is possible to measure death from sodium metabisulfite with available records, its potential morbidity cannot be estimated. It is known that sodium metabisulfite can react with acids and water, releasing toxic sulfur dioxide (SO2) gas. In addition, SO2 gas reacts with respiratory tissue forming sulfureous acid, and inducing a pulmonary reaction causing hypoxemia. Furthermore, sodium metabisulfite, compared with sodium bisulfite, has a much greater propensity to release SO2 gas. We conclude that there is a need for improved education regarding the potential side effects of sodium metabisulfite, thus eliminating needless occupational morbidity and mortality.


Decapoda , Fisheries , Occupational Diseases/chemically induced , Sulfites/adverse effects , Sulfur Dioxide/metabolism , Animals , Asphyxia/chemically induced , Florida , Humans , Male , Melanosis/prevention & control , Seawater , Sulfites/therapeutic use
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