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PubMed1989

A pilot study of the role of prophylactic antiparkinson treatment during neuroleptic therapy.

The authors administered haloperidol 4.5 mg t.i.d. to 33 drug-free schizophrenic patients. Ten patients did not receive anything else (group HPL), while ten patients received procyclidine 5 mg t.i.d., and 13 patients were given promethazine 25 mg t.i.d. (groups HPRC and HPRM respectively) in addition. Seven patients dropped out of the HPL group and three out of the HPRM group, but none out of the HPRC group. These drop outs were due to the development of early extrapyramidal side effects, which were absent in the HPRC group. The findings suggest that antiparkinson prophylaxis is useful during commencement of therapy with high-potency neuroleptic agents.

Adult↗
PubMed1981

Colonoscopy in infancy and childhood with special regard to patient preparation and examination technique.

Only long colonoscopes, Olympus CF-LB2 or TCF-2L, were used for the 76 pediatric colonoscopies. A combination of a thin-liquid diet and laxatives was employed for 1-2 days before all the examinations. Physiological saline enemas on the eve and the morning of the day of examination were employed as supplementary colon-cleansing measures only in larger children. A mixture consisting of chlorpromazine, promethazine and pethidine chloride supplemented with atropine sulfate was used for premedication. Diazepam and ketamine chloride given i.v., or inhalation of halothane +N2O+O2 were employed for general anesthesia. Diazepam and phentanyl citrate given intravenously were used for the sedation of older children. The "classical" and Gaisford's modification of the procedure were found to be the most suitable examination techniques in infants and children. The coecum was reached in 75% of all examinations, and we had no complications with pediatric colonoscopy.

Adolescent↗
PubMed2003

Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study.

BACKGROUND: Loratadine is a second-generation histamine H(1)-receptor antagonist, used in the treatment of allergic conditions. No prospective controlled trials on loratadine in human pregnancy have been published to date. OBJECTIVE: To determine whether the use of loratadine or other antihistamines (OAH) is associated with an increased risk of major anomalies. METHODS: Callers who were counseled by the Israeli Teratogen Information Service in regard to loratadine or OAH exposure during pregnancy were prospectively collected and followed up. Pregnancy outcome was compared among three exposure groups: loratadine, OAH, and a control group of patients who were counseled for nonteratogenic exposure, nonteratogenic controls (NTC). The OAH included astemizole, chlorpheniramine, terfenadine, hydroxyzine, promethazine, and dimetindene. RESULTS: We followed up 210 pregnancies exposed to loratadine (77.9% in the first trimester) and 267 pregnancies exposed to OAH (64.6% in the first trimester) and compared pregnancy outcome with that of 929 NTC. The rate of congenital anomalies did not differ among the groups [loratadine: 4/175 (2.3%), OAH: 10/247 (4.0%), NTC: 25/844 (3.0%), P =.553, relative risk (RR), 0.77; 95% confidence interval (CI), 0.27 to 2.19, (loratadine vs NTC); RR, 0.56; 95% CI, 0.18 to 1.77, (loratadine vs OAH)]. The rate did not differ between those exposed to antihistamines in the first trimester and the control patients [loratadine: 1/126 (0.8%), OAH: 7/146 (4.8%), NTC: 25/844 (3.0%), P =.152, RR, 0.27; 95% CI, 0.04 to 1.94, (loratadine vs NTC); RR, 0.17; 95% CI, 0.02 to 1.33, (loratadine vs OAH)]. CONCLUSIONS: This study on the use of loratadine in human pregnancy suggests that this agent does not represent a major teratogenic risk. The study was powered to find a 3-fold increase in the overall rate of major anomalies.

Abnormalities, Drug-Induced↗
PubMed2002

Treatment patterns of isolated benign headache in US emergency departments.

STUDY OBJECTIVE: I sought to describe and analyze the treatment of a large representative sample of adult US emergency department patients with isolated primary headache. METHODS: Information on adult patients with an isolated diagnosis of migraine headache or unspecified headache was extracted from the 100.4 million ED visits represented by the 1998 National Hospital Ambulatory Medical Care Survey. Demographic and clinical information are presented with descriptive statistics. The treatment of migraine headache was assessed in light of Canadian and US practice parameters. RESULTS: The migraine headache and unspecified headache cohorts included 811,419 and 604,977 participants, respectively. The majority of patients were young, white, and female. Patients received a mean of 1.8 medications from a pharmacopoeia of 36 drugs. Most patients (84.8%) given a diagnosis of migraine headache received a parenteral agent. The most commonly used medications were meperidine (30.0%), ketorolac (21.4%), and prochlorperazine (16.7%). Adjunct antiemetics were commonly administered with parenteral opioids (89.8%). Promethazine and hydroxyzine, antiemetics without anti-headache effects, were used 6 times more commonly as adjuncts than the dopamine antagonists that have established anti-headache effects (ie, prochlorperazine, metoclopramide, droperidol; 78.0% versus 11.8%). The US and Canadian recommendations for the use of nonopioid abortive medications (dopamine-antagonist antiemetics, dihydroergotamine, and 5-hydroxytrypamine(1) [5-HT(1)] receptor agonists) are supported by strong evidence. However, parenterally treated patients with migraines received opioids as their only anti-headache medication more commonly than they received any of the aforementioned non-opioids in their regimen (45.7% versus 26.0%). Of all the opioid recipients, most (77%) did not receive any nonopioid abortive headache medication. Meperidine was the most commonly administered opioid (70%). CONCLUSION: Polypharmacy and a broad pharmacopoeia characterize the US ED treatment of isolated benign headache. Opioid use, particularly meperidine, exceeds that of recommended nonopioid abortive migraine medications.

Administration, Oral↗
PubMed2002

A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis.

STUDY OBJECTIVE: Vomiting in children suffering from acute gastroenteritis interferes with the oral rehydration process and equally frustrates parents and health care providers. Adjuncts such as promethazine and metoclopramide are less than optimally effective and are associated with side effects. Ondansetron, a 5-HT3 receptor antagonist marketed as Zofran, is a safe and effective antiemetic used extensively in oncology and postoperative patients. We evaluate the effect of the antiemetic ondansetron versus placebo on the clinical outcome of patients with vomiting from gastroenteritis in a pediatric emergency department. METHODS: This was a randomized, prospective, double-blind clinical trial in a university-affiliated children's hospital ED. Children between the ages of 6 months and 12 years who had vomited at least 5 times during the preceding 24 hours were randomized to receive either oral ondansetron or a taste- and color-matched placebo. Oral rehydration was commenced 15 minutes later at 5 mL/min per standard oral rehydration protocols. Patients were discharged after they voided and continued standard oral rehydration at home with the introduction of a bananas, rice, applesauce, and toast (BRAT) diet after the first 24 hours. Any patient requiring admission was considered a treatment failure, and no further doses were given. Discharged patients were given 5 additional doses to be used every 8 hours, and they were contacted by telephone 24 and 48 hours after discharge to record the number of episodes of vomiting and diarrhea. The parents were also required to complete a diary of the same information, which was mailed to the investigators for confirmation of the telephone data. RESULTS: One hundred forty-five patients were enrolled, of whom 51% (n=74) were randomized to ondansetron. At baseline, age distribution, sex, and severity of illness did not differ between the ondansetron and placebo groups. During the observation period in the ED, the median number of episodes of vomiting was 0 in both groups, but the rank sum of vomiting episodes was significantly lower in the ondansetron group (P =.001). The number of episodes of emesis in the ED after enrollment ranged from 0 to 7 in the placebo group and 0 to 2 in the ondansetron group. During the 48 hours of follow-up, the median number of episodes of vomiting remained 0, with no statistically significant difference between the groups. There was no statistically significant difference in the rank sum of episodes of diarrhea in the ED between the groups (P =.622); however, during the next 48 hours, the patients in the ondansetron group had significantly more diarrhea than the placebo group. A lower proportion of patients receiving ondansetron compared with placebo required intravenous fluid therapy (P =.015). The admission rate was also lower in patients receiving ondansetron (P =.007). The revisit rate was higher in the ondansetron group compared with the placebo group (P =.047). CONCLUSION: Ondansetron was effective in reducing the emesis from gastroenteritis during the ED phase of oral rehydration and in lowering the rates of intravenous fluid administration and hospital admission.

Acute Disease↗
PubMed2004

Translationally controlled tumor protein is a target of tumor reversion.

By analyzing the gene expression profile between tumor cells and revertant counterparts that have a suppressed malignant phenotype, we previously reported a significant down-regulation of translationally controlled tumor protein (TCTP) in the revertants. In the present study, we derived, by using the H1 parvovirus as a selective agent, revertants from three major solid cancers: colon, lung, and melanoma cell lines. These cells have a strongly suppressed malignant phenotype both in vitro and in vivo. The level of TCTP is decreased in most of the revertants. To verify whether inhibition of TCTP expression induces changes in the malignant phenotype, in the classical, well established model of "flat reversion," v-src-transformed NIH3T3 cells were transfected with antisense TCTP. By inhibiting the expression of TCTP, the number of revertant cells was raised to 30%, instead of the reported rate for spontaneous flat revertants of 10(-6). Because TCTP encodes for a histamine-releasing factor, we tested the hypothesis that inhibitors of the histaminic pathway could be effective against tumor cells. We show that some antihistaminic compounds (hydroxyzine and promethazine) and other pharmacological compounds with a related structure (including thioridazine and sertraline) kill tumor cells and significantly decrease the level of TCTP. All together, these data suggest that, with tumor reversion used as a working model, TCTP was identified as a target and drugs were selected that decrease its expression and kill tumor cells.

Animals↗
PubMed1978

Beneficial and detrimental actions of histamine H1- and H2-receptor antagonists in circulatory shock.

This study explores the use of both histamine H(1)- and H(2)-receptor antagonists in two different forms of circulatory shock and suggests that histamine may be involved in more than one way in the pathophysiology of circulatory shock. Various single doses of diphenhydramine, chlorpheniramine, promethazine, and burimamide were administered intravenously to Wistar rats subjected to hemorrhagic or bowel ischemia shock. Cumulative survival and mortality, as well as arterial blood pressures and microhematocrits, were monitored. Pretreatment of the animals with the three different H(1)-receptor antagonists exerted significant protection against both forms of shock. Rats pretreated with the H(2)-receptor antagonist, burimamide, demonstrated an exacerbated mortality after induction of shock. Animals pretreated with H(1)-receptor antagonists showed significantly higher mean arterial blood pressure, greater compensatory rebound of blood pressure after induction of shock, and greater responses to transfusion after hemorrhage than control, shocked animals. Similarly, rats pretreated with the H(1)-receptor blockers demonstrated significantly greater compensatory hemodilution which continued late in shock. In marked contrast, rats pretreated with burimamide exhibited opposite effects after hemorrhage and bowel ischemia, i.e., significant falls in blood pressure, lack of compensatory rebound and response to transfusion of shed blood, and a progressive hemoconcentration. This report clearly demonstrates beneficial actions of histamine H(1)-receptor antagonists and detrimental effects of H(2)-receptor antagonists on survival and other parameters in these forms of circulatory shock.

Animals↗
PubMed1980

Hypotensive action of parathyroid hormone preparations on rats and dogs.

Bovine parathyroid extract and two commercial preparations containing the first 34 amino acids of synthetic bovine parathyroid hormone [bPTH-(1-34)]produced dose-related hypotension in anesthetized rats. Dogs were 10 times more sensitive to the two bPTH-(1-34) preparations than were rats. Propranolol, phentolamine, atropine, and promethazine did not affect the hypotensive action of bPTH-(1-34) in rats and dogs. bPTH-(1-34) decreased perfusion pressure in rat hindlimbs perfused in situ with Ringer's solution and was a vasodilator in dog kidneys perfused in vitro with Ringer's solution. Helical strips of rabbit aorta were also relaxed by bPTH-(1-34). We conclude that the direct vasodilatory action of bPTH preparations represents an intrinsic property of parathyroid hormone and that the hypotensive effect of this hormone is produced by part or all of the first NH2-terminal 34 amino acids.

Adrenergic alpha-Antagonists↗
PubMed2004

An in vitro study of the effects of Cassia podocarpa fruit on the intestinal motility of rats.

Folkloric evidence and scientific reports indicate the use of C. podocarpa fruit as a purgative recipe. This study attempts to find the in vitro effects of its aqueous infusion (ACPF) and methanolic extract (MCPF) on the motility of the intestine of albino rats of Wistar strain and to compare their effect with those of C. acutifolia fruit (ACAF and MCAF). MCPF relaxed both the ileum and colon dose dependently. Its effect was blocked by tolazoline (10(-9) M) and propranolol (10(-9) M). ACPF had no effect on the ileum, but contracted the colon dose-dependently. Its effect was blocked by nifedipine (2.8 x 10(-10) M) and drastically reduced by atropine (3.4 x 10(-6) M). MCAF has the same effect as ACPF on both ileum and colon and its effect was similarly affected by atropine (3.4 x 10(-6) M) and nifedipine (2.8 x 10(-8) M). ACAF relaxed the ileum, its effect was blocked by tolazoline (5.1 x 10(-7) M). MCAF was more potent than ACPF in contracting the colon, Hexamethonium (2.8 x 10(-8) M), chlorpheniramine (3.8 x 10(-8) M) and promethazine (3.2 x 10(-10) M) potentiated the effect of ACPF on the colon. The results suggest that both ACAF and MCPF have anti-diarrhoeal effect. MCPF acts via both alpha and beta adrenergic receptor stimulation, while ACAF stimulates alpha-receptor. ACPF and MCAF engage both the cholinergic system and calcium channel activation in causing purgation in the colon. The potentiation of the effect of ACPF by some blockers could be due to allosteric enhancement of the receptors involved in its action.

Animals↗
PubMed2005

Mucosal delivery of cytotoxic therapeutic agents: response of rat nasal mucosa to microencapsulated ethopropazine HCl enantiomer.

Use of microencapsulation technology in combination with absorption enhancers eliminated epithelium irritation and necrosis commonly associated with nasal delivery of cytotoxic therapeutic agents. Phenothiazines, such as ethopropazine (ETZ), promethazine, trimeprazine and propiomazine have been used for the treatment of allergenic conditions, motion sickness, nausea, Parkinson's disease, Prion disease and as a sedative for psychiatric disorders. The enantiomers of commercially available racemic phenothiazines were isolated and purified using classical diastereomeric salt techniques. The racemate and the enantiomers of ETZ were tested in vitro for their cellular toxicity using lung fibroblast cells. Each enantiomer was shown to be cytotoxic at concentrations greater than 10(-5) molar. The ETZ enantiomers were encapsulated using spinning disk atomization to prepare a nasal delivery dosage form that does not produce an irritation response. Release rates for the ETZ microcapsules were determined in vitro and an animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated vs. non-encapsulated ETZ.

Animals↗
PubMed2004

Gonadotropin-releasing hormone agonists for prevention of postoperative adhesions: an overview.

Adhesion formation is of major concern to the pelvic surgeon. Most patients develop postoperative adhesions regardless of whether the mode of access to the abdominal cavity is by laparoscopy or laparotomy. Infertility is related to adhesions in the pelvis in 15-20% of cases. Peritoneal adhesions are the main cause of mechanical bowel obstruction in 65-80% of cases and contribute to a large extent to health-care expenditures. To prevent the formation of postoperative adhesions, a variety of medications have been studied such as glucocorticoids, heparin, dextran 70, saline solution, antibiotics, promethazine, antihistamines, prostaglandin synthesis inhibitors, Ringer's lactate solution, calcium-channel blockers and barriers such as Interseed and Gore-Tex. Such adhesions can be induced when operating on myomas and endometriosis. Experimental and clinical studies have demonstrated various mechanisms of action to be involved in adhesion prevention when gonadotropin-releasing hormone agonists (GnRH-a) are used for treatment. The following have been demonstrated and suggested: (1) Hypoestrogenic condition was found in rats to be associated with decreased adhesion formation. This could be related to the influence on estrogen-dependent growth factors and growth modulators by reliable and constant inhibition of ovarian estradiol biosynthesis and secretion, but also non-competitive estrogen antagonism seems to play a role. (2) Treatment with GnRH-a reduces the growth hormone release stimulated by growth hormone-releasing hormone. (3) GnRH-a treatment influences neoangiogenesis by affecting vascular endothelial growth factor and basic fibroblastic growth factor. (4) GnRH-a reduce the basal rate of coagulatory processes. The frequency and extent of fibrin-generating and degrading processes are reduced. Activity of the plasminogen activating inhibitor is reduced, suggesting an improvement infibrinolytic reactivity. (5) GnRH-a use alters the vascular resistance index, pulsatility index and vascular peak velocity, and possible immune response. (6) Avoidance of bleeding can reduce fibrin and therefore decreases the matrix for invasion by fibroblasts. (7) GnRH-a reduce the degree of inflammation postoperatively. Adhesion prevention seems to be at its best when pre- and postoperative GnRH-a treatment is administered. At present, there are trends to operate without prior treatment with GnRH-a. Based upon the data available, it seems worthwhile to consider preoperative and also postoperative treatment with GnRH-a: pretreatment for at least 2-3 months seems to be indicated, and a similar time after operation, to block the events associated with adhesion formation.

Animals↗
PubMed1988

Rate constants for the reactions of halogenated organic radicals.

Absolute rate constants have been measured by means of pulse radiolysis for the reactions of various halogenated aliphatic compounds (ethane derivatives, including the anaesthetics halothane, enflurane, isoflurane and methoxyflurane) with hydrated electrons and .OH radicals, the reactions of halogenated carbon-centered radicals, derived thereby, with molecular oxygen, and the reactions of halogenated peroxyl radicals with various antioxidants (ascorbate, chlorpromazine, promethazine, propyl gallate, ABTS) in aqueous solutions. All oxygen addition reactions occur essentially diffusion-controlled. This finding is correlated with the stereoelectronic properties of the primary carbon-centred radicals. The oxidative power of the halogenated peroxyl radicals reflects the inductive -I effect of the halogens and accordingly increases with the degree of halogen substitution, with fluorine substituents being particularly effective. The peroxyl radicals derived from freon 113, namely CClF2CClFOO. and CCl2FCF2OO., have been identified as the best oxidants among these species.

Anesthetics↗
PubMed1995

Inhibition of radiation-induced changes of glyoxalase I activity in mouse spleen and liver by phenothiazines.

Swiss albino mice (male) were irradiated with gamma-rays at a dose-rate of 0.05 Gy s-1, and the activities of glyoxalase I (GI) and glyoxalase II (GII) were determined after 24 h in the spleen and liver. Radiation up to 4 Gy increased the activity of GI and decreased that of GII. It was possible that the radiation-induced changes in the activity of the glyoxalase system, particularly that of GI, were suggestive of the regeneration status of the tissue. Phenothiazines such as chlorpromazine (CPZ), promethazine (PMZ) and trimeprazine (TMZ) inhibited the radiation-enhanced activity of GI in a concentration-dependent manner. On the other hand, almost no change in the activity of GII was observed using phenothiazines. The effect of phenothiazines on radiation-induced changes of glyoxalase activity were reversed in the presence of ferrous (Fe2+) ions. However, phenothiazines inhibited the radiation effect in the presence of ferric (Fe3+) ions. This combined effect was predominant in the liver. A possible mechanism for the modifying effect of phenothiazines is suggested.

Animals↗
PubMed2000

Local haemorrhage induced by Bothrops jararaca venom: relationship to neurogenic inflammation.

We investigated morphological alterations induced by s.c. injection of 2.5 microg of Bothrops jararaca venom in rats. Intense disorganisation of collagen fibres was observed 1 min after the venom injection, particularly at regions near vessels and nerves. Mast cells were degranulated, and erythrocytes were seen leaving venules throughout the endothelial junctions. At this time, damaged endothelial cells were not observed. In rats envenomed as above, but immediately after cardiorespiratory failure induced by deep ether anaesthesia, alterations in the connective tissue structures, as previously described, were not observed. The mediation of this haemorrhage was investigated by injecting the venom into the foot pad of mice and compared to the mediation of oedema. Local haemorrhage was significantly reduced in mice pre-treated with capsaicin or guanethidine or submitted to a surgical section of sciatic and saphenous nerves. In these animals, oedema was not affected. Groups treated with methysergide or morphine showed both haemorrhage and oedema significantly reduced. Indomethacin or dexamethasone pre-treatments significantly reduced the oedema, but not the haemorrhage. Moreover, in animals treated with promethazine or mepyramine, oedema and haemorrhage were not affected. These data suggest that local haemorrhage induced by Bothrops jararaca venom is partially controlled by serotonin and neurohumoral mediators. Furthermore, results indicate that haemorrhage and oedema are mediated by different pharmacological systems.

Animals↗
PubMed2003

Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers.

Phenothiazine cation radicals (PTZ+*) irreversibly inactivated Trypanosoma cruzi dihydrolipoamide dehydrogenase (LADH). These radicals were obtained by phenothiazine (PTZ) peroxidation with myeloperoxidase (MPO) or horseradish peroxidase (HRP/H2O2) systems. LADH inactivation depended on PTZ structure and incubation time. After 10 min incubation of LADH with the MPO-dependent systems, promazine, trimeprazine and thioridazine were the most effective; after 30 min incubation, chlorpromazine, prochlorperazine and promethazine were similarly effective. HRP-dependent systems were equally or more effective than the corresponding MPO-dependent ones. Chloro, trifluoro, propionyl and nitrile groups at position 2 of the PTZ ring significantly decreased molecular activity, specially with the MPO/H2O2 systems. Comparison of inactivation values for LADH and T. cruzi trypanothione reductase demonstrated a greater sensitivity of LADH to chlorpromazine and perphenazine and a 10-fold lower sensitivity to promazine, thioridazine and trimeprazine. Alkylamino, alkyl-piperidinyl or alkyl-piperazinyl groups at position 10 modulated PTZ activity to a limited degree. Production of PTZ+* radicals was demonstrated by optical and ESR spectroscopy methods. PTZ+* radicals stability depended on their structure as demonstrated by promazine and thioridazine radicals. Thiol compounds such as GSH and N-acetylcysteine, L-tyrosine, L-tryptophan, the corresponding peptides, ascorbate and Trolox, prevented LADH inactivation by the MPO/H2O2/thioridazine system, in close agreement with their action as PTZ+* scavengers. NADH (not NAD+) produced transient protection of LADH against thioridazine and promazine radicals, the protection kinetics being affected by the relatively fast rate of NADH oxidation by these radicals. The role of the observed effects of PTZ radicals for PTZ cytotoxicity is discussed.

Amino Acids↗
PubMed1999

Pharmacological adjuvants during infertility surgery: a systematic review of evidence derived from randomized controlled trials.

The aim of this study was to evaluate systematically the role of pharmacological agents used as adjuvants during infertility surgery to prevent or reduce postoperative adhesion formation and improve pregnancy rates. Meta-analyses were performed of the ten randomized controlled trials identified that evaluated the use of pharmacological adjuvants at infertility surgery. The administration of steroids, dextran 70, noxytioline, heparin, or promethazine have all been investigated for their adjuvant role in preventing adhesion formation during pelvic surgery for infertility. Outcome measures were taken as: pregnancy rates after infertility surgery; number of patients with absent, improved or deteriorated adhesions at second look laparoscopy (dichotomous outcomes); and changes in adhesion score from initial surgery to second look laparoscopy (ordinal outcome). None of the pharmacological adjuncts investigated in a randomized controlled fashion was shown to improve postoperative pregnancy rates. There was some evidence that steroids reduced the incidence or severity of postoperative adhesion formation; there was little evidence to support the use of dextran. The routine use of pharmacological adjuncts during infertility surgery cannot be recommended on the basis of the available evidence derived from randomized controlled trials. Dextran appears to offer no advantage. The evidence with regard to steroids is far from conclusive but tentatively indicates that they may be beneficial.

Journal Article↗
PubMed2004

The influence of anti-irritants on captopril hydrophilic gel.

In this study, we compared the irritation inhibition of various types of anti-irritants such as antihistamines (cyprohetadine, diphenhydramine, and promethazine), alpha-hydroxy acids (gluconolactone and gluco-delta-lactone), corticosteroids (betamethasone and clobetasol), and ion channel modulating agents (amiloride, ethacrynic acid, nifedipine, and verapamil) on the adverse dermatological reaction caused by captopril gel using noninvasive bioengineering methods including measuring the transepidermal water loss (TEWL) and the color change of skin surface [such as change chroma (delta C) and difference in color (delta E) between the gel-treated site and the untreated site]. In addition, the influence of these anti-irritants on the penetration capacity of captopril through the rabbit skin was also investigated. The results showed that the TEWL, change chroma (delta C), and difference in color (delta E) of skin were significantly reduced via incorporating diphenhydramine and clobetasol, indicating that both substances had potent irritation inhibition activity. Moreover, these substances had no effect on the percutaneous absorption of captopril gel. However, flux of the captopril with anti-irritants was about 480 microg/cm2/h and the required minimum administration area to obtain the minimum effective concentration was about 15 cm2, indicating that this formulation could possibly be developed for a transdermal drug delivery system.

Adrenal Cortex Hormones↗
PubMed2001

Assessment of the phototoxic potential of compounds and finished topical products using a human reconstructed epidermis.

The goal of this study was to design a model system for the assessment of phototoxic potential using a human reconstructed epidermis (HRE, SkinEthic Laboratories, Nice, France), by testing some representative phototoxic (P) and non-phototoxic (NP) compounds and finished topical products. The tissue response to 24-h application of 5-5000 microg/mL of the test agents in the presence and absence of UVA light was analyzed in terms of viability (Lactate Dehydrogenase release), pro-inflammatory activity (IL-8 release and mRNA expression) and morphology (histopathology). 8-Methoxypsoralen (P) and promethazin (P), but not sodium lauryl sulfate (NP) produced cytotoxicity concentration-response curves significantly different between irradiated and nonirradiated tissues. Only irradiated tissues showed morphological damage. Application of tetracyclin (P) in the culture medium, but not topically, induced similar signs of phototoxicity. 6-Methylcoumarine (weak P) was not cytotoxic, yet it increased IL-8 release and mRNA expression only following UVA irradiation. PUVA therapy creams containing 1% 8-Methoxy-psoralen (P) or coal tar (P) decreased viability and induced histologic damage in UVA-exposed tissues. In conclusion, the phototoxic potential of the tested agents was correctly predicted by using a tiered strategy that involves determining cytotoxicity, production of IL-8, and morphological damage following exposure of the HRE to the compounds and UVA light.

Cell Survival↗