ABSTRACT
Impaired angiogenesis is a common pathological characteristic of chronic wounds. Therefore, the regulation of angiogenesis is important for proper tissue repair. It was reported that substance P (SP) accelerates wound healing in a skin injury model. SP is degraded by neutral endopeptidase (NEP). Our study shows that systemic co-treatment of SP and thiorphan, an inhibitor of NEP synergically increased the number of α-smooth muscle actin positive-blood vessels in skin wounds. However, there was no synergic improvement in wound contraction and extracellular matrix deposition. Therefore, inhibition of endogenous NEP activity by thiorphan treatment might modulate the effects of SP treatment specifically on accelerating angiogenesis during wound healing. However, the molecular mechanism(s) of the synergic increase in angiogenesis by SP and thiorphan treatment is still unknown.
Subject(s)
Actins , Extracellular Matrix , Neprilysin , Skin , Substance P , Thiorphan , Wound Healing , Wounds and InjuriesABSTRACT
Two accurate and sensitive spectrophotometric and spectrofluorimetric methods were developed for determination of Racecadotril. In the first method reduction of Fe3+ into Fe2+ in presence of o-phenanthroline by Racecadotril to form a stable orange-red ferroin chelate [Fe- [Phen][3][2+] was the basis for its determination. The absorbance at 510 nm was measured and linear correlation was obtained in the concentration range of 2.5 - 25 microg mL[-1]. In the second method the native fluorescence of Racecadotril in acetonitril solvent at lambda, = 319 nm when excitation was at 252 nm is used for its determination. Linear correlation was obtained in the concentration range of 50 to 500 ng mL[-1]. The proposed methods were applied for determination of Racecadotril in bulk powder with mean accuracy of 100.39 +/- 1.239 for the spectrophotometric method and 100.09 +/- 1.042 for the spectrofluorimetric method. The proposed methods were successfully applied for determination of Racecadotril in its pharmaceutical dosage form
Subject(s)
Spectrometry, Fluorescence , Thiorphan/analogs & derivativesABSTRACT
Each year 1.8 million children die due to diarrheal diseases. Indiscriminate use of antibiotics has resulted in increasing resistance to commonly used antibiotics. Moreover the recent outbreaks of shigella and cholera have revealed multi-drug resistance strains. There is a need for review of recommended antibiotics for shigellosis. From recent data it emerges that fluoroquinolones should be the first line of therapy and cephalosporins to be used as the second line. Among the anti-cholera antibiotics, tetracyclines which were the drug of choice for adults, has the advantage of high sensitivity and low cost. Single dose doxycycline would have minimal side effects, hence can be the drug of choice even in children. We should not allow the business pressures to force usage of probiotics and racecadotril as their role in the management of acute diarrhea is yet to be established. Nitazoxanide has high efficacy against Cryptosporodial diarrhea only. Strict adherence to the recommendations for the management of acute childhood diarrhea is needed or else we dilute the effect of standard management.
Subject(s)
Acute Disease , Antidiarrheals/therapeutic use , Antiparasitic Agents/therapeutic use , Child , Child, Preschool , Cholera/drug therapy , Diarrhea/drug therapy , Disease Outbreaks , Dysentery, Bacillary/drug therapy , Female , Humans , Infant , Intestinal Diseases, Parasitic/drug therapy , Male , Probiotics/therapeutic use , Thiazoles/therapeutic use , Thiorphan/analogs & derivativesSubject(s)
Acute Disease , Antidiarrheals/adverse effects , Child , Diarrhea/drug therapy , Drug Evaluation , Female , Humans , Male , Research Design , Thiorphan/adverse effectsABSTRACT
BACKGROUND AND OBJECTIVES: Smoking is regarded as one of the factors that bring about nonspecific hypersensitivity in allergic nasal mucosa. But it is uncertain how chronic smoking affects hypersensitivity in nasal mucosa. This study was designed to evaluate the relationship between smoking and nasal hypersensitivity. In this study, histamine is used since it is commonly used to evaluate nasal hypersensitivity. MATERIAL AND METHODS: Twelve smokers and 9 nonsmokers were participated in this study. Nasal mucosae of each subjects were stimulated by thiorphan followed by substance P. After stimulation, several dilutions of 10 to 5X104 ng/ml of histamine was instilled to both nasal cavity at intervals of 10 minutes. We measured the volume of nasal cavity by acoustic rhinometry in each step and counted the number of sneezing and nasal blowing at every 10 minute intervals. Changes in volume after each dillutions of histamine instillations were compared with the values measured after the stimulation by thiorphan and substance P., and this value was expressed as the percentage volume change. RESULTS: The nasal volume of smoker group was increased upto 100 ng/ml of histamine and decreased from 1000 ng/ml of histamine. The nasal volume of nonsmoker group decreased more than the smoker group with each dilution of histamine. The number of sneezing and nasal blowing increased in each group with each dilution of histamine. CONCLUSIONS: Chronic smoking may decrease susceptibility of hypersensitivity to histamine in nasal mucosa.
Subject(s)
Histamine , Hypersensitivity , Nasal Cavity , Nasal Mucosa , Rhinometry, Acoustic , Smoke , Smoking , Sneezing , Substance P , ThiorphanABSTRACT
The mucus secretion of airway glands is known to be controlled by the various autonomic neurotransmitters such as noradrenalin and acetylcholine. However, a recent study suggests that non-adrenergic, non-cholinergic (NANC) nerves may contribute to the secretory activity of glands. Substance P (SP) has been proposed as a neurotransmitter of the NANC nervous system. SP is present within nerve fibers innervating the airway mucosa and is known to be released from sensory nerves via an axonal reflex. SP activity is controlled by neutral endopeptidase (NEP) which degrades SP. In this study, we evaluated the effects of NEP inhibitor (thiorphan) and substance P on nasal mucosa and histamine on the nasal mucosa in healthy males. In the thiorphan-substance P experimental group, the nasal volume decreased after nebulization of substance P in proportion to the concentration of histamine. In the thiorphan-substance P experimental group, the frequency of sneezing increased in proportion to the concentration of histamine, but there was no increased frequency of sneezing from thiorphan, SP and normal saline. The results of this study suggest that axonal reflexes can play a role in the pathogenesis of nasal mucosal hypersensitivity and neurogenic inflammation.