Carcinoma de células escamosas y el rol discutido de la irritación mecánica crónica. Informe de un caso / Squamous oral cell carcinoma and the discussed role of chronic mechanical irritation. Report of a case

Resumen Objetivo Describir el desarrollo de un carcinoma oral de células escamosas, en el que la irritación mecánica crónica aparenta tomar un rol protagonista en la carcinogénesis. Caso clínico Un paciente de 41 años de edad, argentino, con antecedentes de fisura labio alvéolo palatina, diabetes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odontología del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias semanas de evolución, en íntima relación con un primer premolar superior derecho y una pieza supernumeraria. Se realizó una biopsia y de la anatomía patológica resultó el diagnóstico de carcinoma oral de células escamosas. Se ofreció al paciente posibles tratamientos que rechazó, por lo que se inició terapia paliativa y sintomática. Al avanzar su mal estado general, falleció por complicaciones relacionadas a la deglución. Si bien no está definido el rol de la irritación mecánica crónica en la etiología de la carcinogénesis, ejerce un efecto promotor del daño causado por el tabaco y el alcohol. Si bien el paciente era fumador y bebía alcohol, se puede observar que desarrolló un carcinoma de células escamosas en evidente relación a un trauma crónico, ya que la lesión en la cara dorsal de lengua está en íntimo contacto con el factor irritante. Aun así, la evidencia actual disponible es limitada y discute el protagonismo del trauma crónico por lo que se necesitan más estudios para evaluar y definir la posible relación causal de la irritación mecánica crónica en la carcinogénesis.

Abstract Aim To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation appears to play a significant role in carcinogenesis. Clinical case A 41-year-old patient, from Argentina, with a history of cleft lip and palate, diabetes mellitus, seizures, cocaine and cannabis use, chronic alcoholism and smoking, comes to the Dentistry Service of the Central Hospital for the evaluation of a painful ulcer on the dorsum of the tongue, which had been developing for several weeks, in close relation to an upper right first premolar and a supernumerary tooth. A biopsy was performed, and the pathological anatomy resulted in the diagnosis of oral squamous cell carcinoma. Possible treatments were offered to the patient, which he rejected, so palliative and symptomatic therapy was initiated instead. As his poor general condition progressed, he died due to complications related to swallowing. Although the role of chronic mechanical irritation in the development of carcinogenesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alcohol. Although the patient was a smoker and drank alcohol, it can be observed that he developed a squamous cell carcinoma in obvious relation to a chronic trauma, since the lesion develops on the dorsal face of the tongue in close contact with the irritant factor. Still, the current evidence available is limited and discusses the role of chronic trauma, so more studies are needed to evaluate and define the possible causal relationship of chronic mechanical irritation in the development of carcinogenesis.

Effects and mechanism of Curcumin solid lipid nanoparticles loaded with flower-shaped lactose for inhalation on pulmonary inflammation in COPD model mice / 中国药房

OBJECTIVE To investigate the effects and mechanism of curcumin （Cur） solid lipid nanoparticles （SLN） loaded with flower-shaped lactose （Cur-SLN-FL） for lung inhalation on lung inflammation in chronic obstructive pulmonary disease （COPD） model mice. METHODS Firstly， the irritation of Cur-SLN-FL to lung tissue was investigated， and the local safety of inhalation materials was determined. Then， 10 mice were randomly selected and injected with normal saline through the trachea， and the other 50 mice were all injected with porcine trypsin solution （concentration of 33.3 mg/mL， dosage of 1.0 mL/kg） to induce the COPD model. After normal feeding for 28 days， the mice were divided into sham operation group， model group， budesonide group （20 mg/kg）， Cur-SLN-FL high-dose and low-dose groups （100， 50 mg/kg）， with 10 mice in each group. The corresponding drugs were given to each group， once a day， for 14 consecutive days. Twenty-four hours after the last administration， the bronchoalveolar lavage fluid （BALF） of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin （HE） staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 （NLRP3）， caspase-1 and interleukin-1β （IL-1β） in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3， caspase-1 and nuclear factor of kappa B（NF-κB） in lung tissue. RESULTS Cur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group， the total number of white blood cells， neutrophils and eosinophils in BALF of the model group increased significantly， while the number of lymphocytes decreased significantly （P＜0.05）； ciliated columnar epithelium proliferated， thickened and exfoliated in the trachea， mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue；the deposition of collagen fibers in lung tissue increased significantly， the positive expressions of NLRP3， caspase-1 and IL-1β in lung tissue increased significantly， and the expressions of NLRP3， caspase-1 and NF-κB protein in lung tissue all increased significantly （P＜0.05）. After giving Cur-SLN-FL， the above indexes were all improved to certain extent. CONCLUSIONS Cur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice，and its mechanism may be through regulating the NLRP3 signaling pathway， inhibiting the expressions of caspase-1， NF-κB and IL-1β， thus alleviating the process of pulmonary fibrosis in COPD model mice.

GC-MS Analysis of Effect of Different Processing Conditions on Irritation of Magnoliae Officinalis Cortex / 中国实验方剂学杂志

ObjectiveTo investigate the key compounds affecting the irritation and to clarify the effect of heating and the addition of ginger juice as the auxiliary material during the processing on the irritation of Magnoliae Officinalis Cortex（MOC） by comparing the irritation and composition of volatile oil in MOC and its different processed products. MethodVolatile oil in raw products， water-processed products， ginger-dried products， ginger-fried products（the amounts of ginger were 10%， 50%， respectively） of MOC were extracted by steam distillation and subjected to rabbit eye irritation experiment， and the volatile components of each sample were detected by gas chromatography-mass spectrometry（GC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to analyze the data of each sample by SIMCA 14.1. The relative contents of different processed products were compared two by two with those of and raw products or ginger-fried products， and the markers that might be related to the irritation were sorted out according to the principles of variable importance in the projection（VIP） value >1 and P<0.05， and the factors influencing the differences in irritation were analyzed. ResultCompared with the blank group， the administration groups all had irritation to the eyes of rabbits， and the degree of irritation was in the order of raw products>water-processed products>ginger-dried products>ginger-fried products（10%）>ginger-fried products（50%）. The results of PCA and OPLS-DA showed that there were differences in the volatile oil from raw products and different processed products. According to VIP value>1 and P<0.05， and combined with the results of eye irritation experiment， ten volatile compounds related to irritation changes were screened out. Among them， cis-cinnamaldehyde was only detected in raw products， the relative contents of β-caryophyllene， （+）-delta-cadinene， α-humulene， γ-muurolene， （-）-isoledene and citral all increased to different degrees， the contents of p-cymene， 1（10）-4-cadinadien-15-ol and β-eudesmol all decreased to different degrees. ConclusionThe irritation of MOC is reduced after heating and processing with ginger juice， and the synergistic effect of both is more effective for reducing irritation. Among the differential markers associated with changes in irritation， the increase in the relative content of citral is closely related to the addition of ginger juice， while the decrease in the relative contents of cis-cinnamaldehyde， p-cymene， 1（10）-4-cadinadien-15-ol is related to heating， and the changes of other components may be related to the synergistic effect of heating and ginger juice.

The eye irritation test and pharmacokinetic study of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits / 药学实践杂志

Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.

Application of bovine corneal opacity and permeability test in the eye irritation evaluation of cosmetics / 上海预防医学

Objective To establish bovine corneal opacity and permeability （BCOP） test， and determine its predictive ability for the eye irritation evaluation of cosmetics. Methods A total of ten reference chemicals were selected to establish the BCOP test. Then eye irritation of 16 routinely collected cosmetics in our laboratory was predicted. In vitro scores were calculated by the change in the opacity and sodium fluorescein permeability after exposure to the testing cosmetics， and subsequently compared with the historical data by Draize test. Results Reference chemicals with known irritation classification were correctly classified by the BCOP test， which was consistent with the classification of UN globally harmonized system of classification and labeling of chemicals. Moreover， the specificity of the BCOP test for the classification of non-irritating cosmetics samples was 80.0% （8/10）， and the sensitivity for weak to mild irritating cosmetics samples was 83.3% （5/6）. The BCOP test demonstrated an overall classification consistency of 81.3% （13/16） with in vivo test. Conclusion BCOP test may be independently used to identify chemicals with potential eye irritation and serious eye damage， suggesting it is significant for in vitro integrated test strategy for predicting eye irritation due to cosmetics.

A Case of Excessive Sweating and Hot Flushes Successfully Treated with Yokukansan / 日本東洋医学雑誌

We report a case of a 49-year-old woman who presented with 6-month period menopausal syndrome including excessive sweating and hot flushes in her face, chest and back. She was also frustrated with her sons, but she reflected on her own anger and wondered why she got so irritated with them. We prescribed yokukansan to her and her all symptoms improved one month later. We need to differentiate between yokukansan and kamishoyosan in the treatment of menopausal syndrome and irritation, and it may be useful to evaluate the detail of irritation in selecting formula.

Development and evaluation of topical formulations that contain hydroethanolic extract from Schinus terebinthifolia against HSV-1 infection

Abstract The therapeutic drugs to treat Herpes simplex virus (HSV) infections have toxic side effects and there has been an emergence of drug-resistant strains. Therefore, the search for new treatments for HSV infections is mounting. In the present study, semi-solid formulations containing a crude hydroethanolic extract (CHE) from Schinus terebinthifolia were developed. Skin irritation, cutaneous permeation, and in vivo therapeutic efficacy of the formulations were investigated. Treatment with the ointment formulations did not result in any signs of skin irritation while the emulsions increased the thickness of the epidermis in Swiss mice. The cutaneous permeation test indicated that the CHE incorporated in the formulations permeated through the skin layers and was present in the epidermis and dermis even 3 h after topical application. In vivo antiviral activity in BALB/c mice treated with the CHE ointments was better than those treated with the CHE emulsions and did not significantly differ from an acyclovir-treated group. Taken together, this suggests that the incorporation of CHE in the ointment may be a potential candidate for the alternative topical treatment of herpetic lesions.

Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism / 中国中药杂志

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Scientific Analysis of Processing of Pinelliae Rhizoma by Ancient Hot Water Washing Method / 中国实验方剂学杂志

Objective:To evaluate the scientificity and feasibility of processing of Pinelliae Rhizoma by hot water washing （Tangxi）， and to provide reference for the development of related famous classical formulas. Method:Processing method of Pinelliae Rhizoma washed by hot water was established based on ancient Tangxi processing method， and the process conditions were optimized by single factor tests. The weight， moisture， ash， extract， total acid （calculated by succinic acid） contents and high performance liquid chromatography （HPLC） fingerprint of Pinelliae Rhizoma were compared before and after processing. In addition， the rabbit eye irritation test was conducted to evaluate the toxicity changes. Result:The processing method of Pinelliae Rhizoma washed by hot water was as following：washed by 4 times the amount of hot water at 80 ℃ for 10 times until clear water， transfused cross-section after incision， no or slight numbness in the mouth. The average moisture， ash， extract contents of Pinelliae Rhizoma washed by hot water were 9.34%， 1.71% and 4.22%， respectively. After being processed， the decline rates of weight and total acid content of Pinelliae Rhizoma were 7.49% and 43.31%. The HPLC fingerprint of Pinelliae Rhizoma before and after washing showed a decrease in all components， but there was no new chromatographic peak， and peak 9 （adenosine） reduced significantly. The results of rabbit eye irritation test showed that there was no obvious eye conjunctival irritation after washing， indicating that the toxicity of Pinelliae Rhizoma decreased obviously after washing. Conclusion:The established method of Pinelliae Rhizoma by Tangxi processing is stable and feasible， the aqueous extract of Pinelliae Rhizoma has no obvious eye conjunctival irritation after washing.

Research progress on Er: YAG lasers applied for tooth bleaching / 口腔疾病防治

@#Er: YAG laser bleaching is a new tooth bleaching method compared with traditional bleaching technology. The Er: YAG laser significantly improves the bleaching efficiency, has the advantages of high safety, short treatment time and excellent bleaching effect and is widely used in clinical operations. This paper summarizes the working principle and bleaching characteristics of Er: YAG laser bleaching technology and its effect on tooth structure. The existing literature suggests that the high absorption of water and hydroxyapatite by the Er: YAG laser makes it work well on water-bearing tissues and dental tissues. When it is absorbed by the bleaching agent on the tooth surface, it accelerates the catalytic oxidation-reduction reaction and selectively acts on the pigment particles deposited on the tooth, thereby achieving the effect of tooth bleaching. Er: YAG laser bleaching can be applied to most discolored teeth. The bleaching process is rapid and effective. During the bleaching process, for the dental pulp tissue, the temperature of the pulp cavity is lower than the critical value of 5.6 ℃, causing no pathological damage to the dental pulp tissue. For the hard tissues of the teeth, laser irradiation will cause changes in the chemical composition of calcium and phosphorus. The enamel presents a unique lava-like shape, and the bonding strength of the tooth increases after bleaching. Compared with other lasers, the Er: YAG laser has a wavelength close to the peak of water, and adding other ingredients to the bleaching agent is not required. Almost all the energy is used for the bleaching agent, with no damage to the surrounding tissues.

A target lipidomics approach to investigate the acute inflammatory irritation induced by indolealkylamines from Chansu water fraction in rats / 中国天然药物

Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT

Antimicrobial and wound healing activity of Ixora coccinea leaf extract in hydrogel formulation

@#<p style="text-align: justify;"><strong>Objectives.</strong> The purpose of this study was to evaluate the antimicrobial and wound healing property of the preformulated hydrogel containing the methanolic leaf extract of Ixora coccinea, as well as its acute dermal irritation using New Zealand rabbits.</p><p style="text-align: justify;"><strong>Methods.</strong> Mature dried leaves of I. coccinea was subjected to extraction using maceration and was concentrated in vacuo. Sodium carboxymethylcellulose and gelatin were used to create hydrogel in which the crude extract was incorporated. Physicochemical properties of the extract and preformulated hydrogel were characterized, while its antimicrobial activities against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis were determined using the agar well method and compared to the standard drug 2% w/v mupirocin ointment. A wound excision model in rats was used to determine the wound healing property of the preformulated hydrogel against povidone-iodine ointment. Lastly, animal testing was performed following the OECD Guidelines and upon approval of the IACUC Committee.</p><p style="text-align: justify;"><strong>Result.</strong> The preformulated hydrogel was effective against S. aureus (p-value ? 0.001) but resistant to P. aeruginosa and S. epidermidis. Furthermore, the wound contraction rate in groups treated with preformulated hydrogel (p-value = 0.006) is significantly higher than in groups treated with hydrogel base and povidone-iodine. Moreover, no dermal erythema and edema were observed with albino rabbits.</p><p style="text-align: justify;"><strong>Conclusion.</strong> The preformulated hydrogel with I. coccinea methanolic leaf extract is non-irritating, effective against staphylococcal infections commonly found in wounds. Hence, it is a good substitute for povidone-iodine in wound treatment.</p>

Assessment of the Dermal Acute Irritation Potential of Natural Veterinary Medicine Minyak Rajas in Albino Rabbits

Aims: This study was designed to assess the potential for acute dermal irritation of natural veterinary medicine Minyak Rajas (produce by SonggolangitPersadaLimited Company, Bali, Indonesia) in albino rabbits. It is a rather thick liquid which contains various medicinal herbal extracts, formulated with effective microorganism technology. This medicine is effective in the treatment of skin infections and inflammation, wounds, intestinal worms and digestive disorder. Additionally, it works for game fowl muscle strengthening.Place and Duration of Study:This study was conducted at the Veterinary Pharmacy and Pharmacology Laboratory, Faculty of Veterinary Medicine, Udayana University, between April 2020 and May 2020.Methodology:Experimental animals used were three male albino rabbits (Oryctolaguscuniculus) in healthy conditions and weighing of >2 Kg. Test procedures followed the guidelines of Organisation for Economic Cooperation and Development, and chemicals used were applied in a single dose of 0.5 ml on animal skins, with untreated skin as a control.Results:Very slight erythema was found after the Minyak Rajas application and the lesion was about 48 hours.Overall, no severe erythema, edema or other skin lesions were observed. According to the AmandedDraize system, the Primary Irritation Indexes of 0.16 is categorized as non-irritating.Conclusion:We conclude that the natural veterinary medicine of MinyakRajasis safe to be used

Development And Characterization Of Liposomal Formulation For Ophthalmic Delivery Of Prednisolone Acetate

Liposomal vesicular drug carriers for ocular delivery have earned a wide potential nowadays. Prednisolone Acetate liposome as ocular drug carriers have been demonstrated to be a useful mode to ameliorate bioavailability and patient abidance. Liposome was prepared by lipid extruder method. Liposome were characterized for entrapment efficiency (EE %), vesicle size, surface morphology and in vitro drug release. An ex vivo corneal permeation study was performed to determine the level of drug in the external eye tissue of goat and an ocular irritation assessment was done by Hen’s Egg Test - Chorioallantoic Membrane (HET-CAM) method. The optimized formulation of liposome had shown acceptable viscosity (1.21 ± 0.03 cps), refractive index (1.47±0.001), osmolarity (303 ± 3 mOsm) and pH measurement (7.12 ± 0.09). Liposome as drug delivery carriers were evidenced to be a anticipating impendent to enhance corneal contact and penetration as well as retention time in the eye ensuing in a prolonged action and enhanced bioavailability. The results of stability study exhibited stable profile of developed liposomes.

Effect of transcutaneous electrical acupoint stimulation on catheter related bladder discomfort after ureteroscopic lithotripsy / 中国针灸

OBJECTIVE@#To verify the efficacy of transcutaneous electrical acupoint stimulation (TEAS) on catheter related bladder discomfort after ureteroscopic lithotripsy.@*METHODS@#Sixty male patients with selective ureteroscopic lithotripsy under general anesthesia were randomly divided into a TEAS group (30 cases, one case dropped off) and a sham TEAS group (30 cases, 2 cases dropped off). Before anesthesia induction, the patients in the TEAS group were treated with TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) for 30 min, with disperse-dense wave, frequency of 2 Hz/ 15 Hz and current intensity of 6 to 10 mA. The patients in the sham TEAS group were treated with the same TEAS device at the same acupoints, but no electrical stimulation was given. After 30 min, anesthesia induction started. The total dosages of propofol and remifentanil in the two groups were recorded, and the time of operation and anesthesia, the time of wake-up and the time of stay in postanesthesia care unit (PACU) were recorded. The postoperative recovery was evaluated 5 min (T) after wake-up, 1 h (T), 2 h (T) and 6 h (T) after the operation, including the severity of urinary tract irritation and visual analogue scale (VAS) score. The occurrence of adverse reactions was observed, such as nausea and vomiting, dizziness and headache.@*RESULTS@#The dosage of remifentanil in the TEAS group was significantly lower than that in the sham TEAS group (0.05). Compared with the sham TEAS group, the incidence of more-than-moderate urinary tract irritation symptoms in the TEAS group was reduced (<0.05), and the VAS scores 1 and 2 h after operation were reduced (<0.05).@*CONCLUSION@#The 30-min TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) before anesthesia induction could significantly control the severity of postoperative urinary tract irritation in patients with ureteroscopic lithotripsy, reduce the dosage of anesthetic drugs and relieve postoperative pain.

Study on Skin Irritation of Clobetasone Butyrate Cream in Rabbits and Its Skin Sensitization in Guinea Pigs / 中国药房

OBJECTIVE：To study the skin irritation and se nsitization of domestic generic drug Clobetasone butyrate cream ， and to compare it with commercial drug （original drugs ）. METHODS ：The skin irritation test was conducted on rabbits. Totally 24 rabbits were randomly divided into test preparation intact skin group ，test preparation abraded skin group ，commercial drug intact skin group and commercial drug abraded skin group ，with 6 rabbits in each group. 0.5 mL test preparation or commercial drug was administered to the left side of intact or abraded skin and the same amount of excipient on the right side of each rabbit twice a day for consecutive 7 days. The irritation of the drug to the rabbit skin was observed ，and the erythema and edema of the skin were scored；the skin of administration site was taken at 72 h after last administration and the end of 7 d after drug withdrawal for histopathological examination. The skin sensitization test （Buehler test ）was carried out on guinea pigs. Totally 60 guinea pigs were randomly divided into test preparation group （n＝20），commercial drug group （n＝20），positive control group （n＝10）and excipient control group （n＝10）. 0.2 mL test preparation or commercial drug was administrated to the left side of the rib abdomen skin of each guinea pig at the 0，7th，14th day to induce model ，and an equal amount of corresponding preparation was administered to the right side in the same way at the 28th day for stimulation. Hypersensitive response such as erythema and edema were observed and scored at 24 h and 48 h after the stimulation. The incidence of hypersensitive response was then calculated. RESULTS：In skin irritation test of rabbits ，no erythema and edema was caused by the test preparation or commercial drug on intact skin of rabbits ；scores of skin irritation was 0；there was no dermal irritation. Both test preparation and commercial drug caused transient slight erythema on abraded skin of a few rabbits ；scores of intact and abraded skin irritation were 0-0.33；there was no dermal irritation. There was no statistical significance among groups. No dermal pathological changes were observed. In skin sensitization test of guinea pig ，no hypersensitive response such as erythema and edema was found on the skin of guinea pigs in both test preparation and commercial drug groups ；both score and the incidence of hypersensitive response were 0. Compared with excipient control group ，there was no statistical significance of average score and the incidence of hypersensitive response in test preparation group and commercial drug group. CONCLU- SIONS：In skin irritation test of rabbits and skin sensitization test of guinea pigs ， the evaluation results of generic Clobetasone butyrate cream are the same as those of the original drug. It has no irritation to the skin of rabbit ，and no sensitization to the skin of guinea pigs.

A rational pharmacotherapeutic study of comparative safety among topical anti-acne 1% nadifloxacin monotherapy, 0.1% adapalene monotherapy, 0.025% tretinoin monotherapy, 1% nadifloxacin and 0.1% adapalene combination therapy and 1% nadifloxacin and 0.025% tretinoin combination therapy, in mild to moderate acne vulgaris, in tertiary care hospitals

Background: Topical adapalene and tretinoin, are comedolytic, anti-comedogenic and anti-inflammatory, on RAR (?, ?, ?) receptors binding. Adapalene enables quicker follicular penetration, by lesser anti-AP-1 (c-Jun, c-Fos) and no CRBPII mRNA actions, causing chemical stability, lipophilicity and less photo-lability, producing lesser photosensitivity and no skin irritation, unlike tretinoin; wherein reducible by overnight application and combination therapy, slow-release polymers or emollients, respectively. Topical nadifloxacin is bactericidal, anti-inflammatory and comedolytic, with inhibitory effect on DNA gyrase, DNA topoisomerase IV and IL-1?, IL-6, IL-8. The Global Alliance to Improve Outcomes in Acne Guidelines recommend synergistic and additive combination therapies, which enhance therapeutic efficacy and reduce adverse effects. Due to inadequacy of data, this study was conducted, to compare the safety among topical anti-acne monotherapies and combination therapies, and to easily detect any adverse effect producing component in the topical combination therapy.Methods: In this multi-centre, prospective, randomised, open-labelled, comparative study, groups A, B, C, D and E (20 patients each), applied topical 1% nadifloxacin monotherapy, 0.1% adapalene monotherapy, 0.025% tretinoin monotherapy, 1% nadifloxacin and 0.1% adapalene combination therapy and 1% nadifloxacin and 0.025% tretinoin combination therapy, respectively, over their facial mild to moderate acne lesions, once daily overnight; and adverse effects, like erythema, scaling, dryness, prutitus, burning, or stinging, were assessed on 0, 15, 30, 60, 90 days and follow-ups, by Local Irritation Scale.Results: In all 5 groups, no adverse effects were observed, with no statistically significant difference among the observations.Conclusions: The therapies were well tolerated and safe among all 5 groups.

Constellation of Oral Inflammatory Hyperplastic Lesions: Case Series with Review of Literature

Oral cavity, when subjected to various forms of chronic insults or microtrauma, often results in a hyperplastic lesion, commonly referred to as inflammatory reactive hyperplasia. This category includes various lesions such as peripheral fibroma, peripheral ossifying/cementifying fibroma, pyogenic granuloma, and peripheral giant cell granuloma. They are primarily seen to develop in close proximity to the source of chronic irritant and have a close resemblance in terms of biological behavior and clinical presentation. Histopathologically, they display a common feature of hyperplastic fibrous tissue, but also have some variations like the presence of giant cells or aggregate of calcified mass depending on the histogenesis of the lesion. They were the most common tumor-like lesions to be seen in the oral cavity, familiarity with these lesions are of utmost importance. The present article portrays a series of 5 cases of different clinical forms of reactive hyperplasia with a brief literature review. The current manuscript is presented with an aim to enhance the knowledge about hyperplastic lesions.

In Vivo Evaluation Of Tazarotene Solid Lipid Nanoparticles Gel For Topical Delivery

The purpose of this research work was to develop and optimize the Solid Lipid Nanoparticles (SLNs) of Tazarotene for the effective topical delivery in the treatment of psoriasis. Tazarotene loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s design and based on the results further investigation was made using central composite design. The lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, TEM, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. In vitro drug release of optimized SLN formulation (F1) was found to be 98.12 ± 1.52%, whereas pure drug release was 42.12 after 60 min. The optimized formulation was incorporated into the gel. The release rate (flux) of tazarotene across the membrane and excised skin differs significantly. The accumulative amount of Tazarotene in skin from SLN based gel formulation and marketed gel were 41.12 ± 0.12 mg and 30.02 ± 0.04 mg respectively. This result supported our hypothesis made in skin permeation studies on rat skin. From histopathological studies the microscopic observations indicate that the optimized SLN formulation, SLN based gel formulation and marketed gel has no significant effect on the microscopic structure of the skin. The skin-irritation studies indicated that SLN based gel containing Tazarotene did not show any sign of skin irritation as compared to moderate erythema shown by marketed gel formulation (Tazret® gel) after 72 h of application. Thus, SLN based gel formulation demonstrated advantage over marketed formulation in improving the skin tolerability of Tazarotene indicating their potential in improving patient acceptance and topical delivery of Tazarotene.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.