Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma cells （PC12） in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Alzheimer＇s presenilin-1 （PS 1） mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intracellular calcium homeostasis and thus being less potent pared the cytotoxic effects of various inhaled to cause cytotoxicity. This study examined and com-anesthetics on PC12 cells transfected with the Alzheimer＇s mutated PS 1 （L286V） and the disruption of intracellular calcium homeostasis. PC 12 cells transfected with wild type （WT） and mutated PS 1 （L286V） were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space （[Ca^2＋]c） were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca^2＋]c in L286V than in the WT cells. Xestospongin C significantly ameliorated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in L286V PC 12 cells. These results suggested that isoflurane induced cytoxicity by partially causing abnormal calcium release from the ER via activation of IP3 receptors in L286V PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar elevation of [Ca^2＋]c or neurotoxicity in PC 12 cells transfected with the Alzheimer＇s PS 1 mutation.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Inhaled volatile anesthetics in the intensive care unit

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care settings.In the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status epilepticus.Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor therapy.Furthermore,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation modalities.Despite the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe use.This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

Clinical Efficacy Analysis of Tiotropium Bromide Combined with Budesonide and Formoterol Inhalation in Treating COPD

Objective:To analyze the clinical efficacy of tiotropium bromide(TB)combined with budesonide formoterol(BUD/FM)inhalation in treating chronic obstructive pulmonary disease(COPD).Methods:62 COPD patients admitted to the hospital between June 2020 and December 2022 were selected as samples for this study.The patients were divided into a combination group and a conventional group using the random number table method,with 31 cases in each group.The patients in the combination group were treated with TB combined with BUD/FM inhalation,whereas the patients in the conventional group were treated with BUD/FM inhalation only.The treatment efficacy and changes in lung function indicators of both groups were compared.Results:The total efficacy of treatment in the combined group was higher than that in the conventional group,and the difference was statistically significant(P<0.05).Before treatment,there was no difference in pulmonary function indicators between the two groups(P>0.05).After three months of treatment,all lung function indicators of the combined group were higher than those of the conventional group,and the difference was statistically significant(P<0.05).Conclusion:Combining TB with BUD/FM inhalation therapy increases the efficacy of treatment for patients with COPD.Besides,it also improves lung function and leads to a better prognosis.

Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods

Although the GABAA receptor(GABAAR)has been proposed as the main action site for sevoflurane,isoflurane,halothane,enflurane,propofol,and benzodiazepines(BZDs),binding of these anesthetics with high-resolution structures of the GABAAR have been rarely examined by comparative docking analyses.Moreover,various combinations of ligands on more GABAARs with various subtypes need to be analyzed to understand the elaborate action mechanism of GABAARs better because some GABAA ligands showed specificity toward the distinct subtypes of the GABAAR.Methods:We performed in silico docking analysis to compare the binding modes of sevoflurane,isoflurane,halothane,enflurane,propofol,and BZDs to the GABAAR based on one of the most recently provided 3D structures.We performed the docking analysis and the affinity-based ranking of the binding sites.Results:Our docking studies revealed that isoflurane,halothane,and enflurane docked in an extracellular domain(ECD)on GABAARs,in contrast to sevoflurane.Conclusion:Our results supported a multi-site mechanism for the allosteric modulation of propofol.Propofol was bound to the pore or favored various subsites in the transmembrane domain(TMD).Our result confirmed that different chemically related BZD ligands interact via distinct binding modes rather than by using a common binding mode,as previously suggested.

The Effect of Nebulized Budesonide Inhalation in Treating Children with Asthma and its Influence on Immune Indexes

Objective:To explore and analyze the effect of nebulized budesonide inhalation on children with asthma and its influence on immune indexes.Methods:300 children who were with asthma admitted to the Pediatric Respiratory Department of our hospital from January 2021 to January 2023 were selected as the research subjects.The patients were divided into a nebulization group(n=150)and a reference group(n=150)by drawing lots.The nebulization group received routine treatment along with budesonide nebulization inhalation therapy,while the reference group only received routine treatment.The treatment effect,the immune indicators,the time taken for the disappearance of symptoms,and the pulmonary function indicators of both groups were compared.Results:The total efficacy of treatment received in the nebulization group was significantly higher than that in the reference group(P<0.05).Before treatment,there was no statistically significant difference in the CD4^(+),CD8^(+),CD4^(+)/CD8^(+),between the two groups(P>0.05);after treatment,the nebulization group’s CD4^(+),CD8^(+),CD4^(+)/CD8^(+)and other immune indicators were significantly better than the reference group(P<0.05).The time taken for the disappearance of symptoms like wheezing,coughing,crackles,shortness of breath,and other symptoms in the nebulization group was significantly shorter than in the reference group(P<0.05).Before treatment,there was no statistically significant difference in the pulmonary function indexes such as FEV1,PEF,and FVC between the two groups(P>0.05);after treatment,the pulmonary function indexes of the patients in the nebulization group were significantly better than those in the reference group(P<0.05).Conclusion:Nebulized budesonide inhalation therapy has shown significant efficacy in the treatment of pediatric asthma,with notable improvements in immune indicators.Therefore,it is worthy of recommendation and further promotion.

Recent progress of respiratory inhalation drug delivery systems

With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.

Adjuvants to local anesthetics: Current understanding and future trends

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).

Why Labor Epidural Causes Fever and Why Lidocaine Burns on Injection? Role of TRPV 1 Receptor in Hyperthermia: Possible Explanation of Mechanism of Hyperthermia during Labor Epidural and Burning Sensation on Injection of Local Anesthetics

The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor can explain this effect and explain mechanism of burning sensation on local anesthetic injected subcutaneously or intramuscular. Role of TRPV1 receptor was not discussed previously in Obstetric Anesthesia literature. Based on available data, we propose that Local Anesthetics work as agonist/antagonist on TPRV1 receptors. Antagonist action may cause hyperthermia through modifying thermoregulation [4], agonist action may cause hyperthermia thru release of IL-6 and other mediators of inflammation [5-10]. Agonist action may explain burning sensation on injection of Local Anesthetics. Burning sensation can be diminished by increasing pH of Local Anesthetic solution, because vanillin receptors are stimulated by acidification through lower pH [11,12].

Nitrogen monoxide vector of ultrasonic atomizing inhalation improves vertebro-basilar artery insufficiency Hemodynamic changes are detected by transcranial Doppler test

BACKGROUND： Latest researches at home and abroad indicate that glycerol trinitrate plays its function because it can metabolize into nitrogen monoxide （NO） in vivo. OBJECTIVE： To study the therapeutic effects of NO vector of ultrasonic atomizing inhalation on vertebro-basilar artery insufficiency （VBI） through transcranial Doppler （TCD） detection and serum NO content and indirect effect of TCD on cerebral blood flow changes. DESIGN： Randomized grouping and controlled clinical study. SETTING： Department of Neurology, the Fourth People＇s Hospital of Jinan. PARTICIPANTS： A total of 130 patients who were diagnosed as VBI were selected from Department of Neurology, the Fourth People＇s Hospital of Jinan from December 2001 to December 2005. The involved inpatients were checked by CT and MRI, and met the VBI diagnostic standard enacted by the Fourth National Academic Meeting of Cerebrovascular Disease in 1995. All patients and their relatives provided the confumed consent. They were randomly divided into low-dose treatment group （n =60）, high-lose treatment group （n =30） and control group （n =40）. METHODS： Patients in the low-dose and high-dose treatment groups were given ultrasonic atomizing inhalation of 3 mg and 5 mg glycerol trinitrate, respectively, for 20 minutes, once a day. In addition, ligustrazine and energy mixture were used once a day for three days in a course. Cases in the control group were only given ligustrazine and energy mixture. All selected cases accepted TCD, blood NO content was checked at the time of beginning, after the first time and after a period of treatment. According to the TCD test, VBI patients were divided into two groups （high-low flow velocity）. The vertebral artery （VA） and basal artery （BA） of left or right sides were detected by 2 Hz detector via occipital window. MAIN OUTCOME MEASURES： ①Blood flow velocity of systolic phase, blood flow velocity of diastole phase and vascular resistance in left and right VA and BA detected by using TCD before treatment, after treatment for one course; ②content of serum NO indirectly measured by using nitric acid disoxidation technique. RESULTS： All 130 VBI patients were involved in the final analysis. ①Changes of hemodynamic indexes： Systolic phase of VA and diastole phase of BA were higher in low-dose treatment group than that in the control group after first treatment, and there was significant difference （P 〈 0.05）; meanwhile, systolic phase and diastole phase of VA and systolic phase of BA were also higher in treatment group than that in the control group after one course （P 〈 0.05）. However, both systolic phase and diastole phase of VA and BA were lower in high-dose treatment group than that in the control group after first treatment and one course, and there was significant difference （P 〈 0.05）. ②Content of serum NO： After first treatment, there was no significant difference between low-dose treatment group and high-dose treatment group （P 〉 0.05）; but both groups were higher than control group, and there was significant difference （P 〈 0.05, 0.01）. CONCLUSION： NO vector of ultrasonic atomizing inhalation can improve VBI so as to improve cerebral blood-supply state.

Anesthetic Action of Volatile Anesthetics by Using Paramecium as a Model

Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells （denoted as Iche） was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.

Studies on the spray dried lactose as carrier for dry powder inhalation

The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation(DPI).The lactose particles were prepared by spray drying,then the particle size,shape and crystal form were characterized by laser diffraction,scanning electron microscopy(SEM),X-ray diffraction(XRD)and differential scanning calorimetry(DSC).The spray dried lactose particles were spherical and amorphous,but would transfer to crystal form when storage humidity was above 32%.Thus,the humidity of the storage environment should be controlled below 30%strictly in order to maintain the amorphous nature of spray dried lactose which is a great benefit to DPI development.

The Protective Effects of Preventive Atomisation Inhalation of Edaravone on the Lung Tissues of Rats with Smoke Inhalation Injury

Objective: To investigate the protective effects of the atomisation inhalation of edaravone on the lung tissues of rats with smoke inhalation injury. Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups of ten rats each: normal control group (group A), normal saline atomisation group (group B), edaravone aerosol group (group C) and edaravone atomisation prevention group (group D). Barring group A, the groups were used to create a model of severe smoke inhalation injury. However, before developing the model, group D rats were made to inhale edaravone (3.6 mg/mL) for 10 min. Six hours following smoke inhalation injury, abdominal artery blood samples were centrifuged, the lung tissue homogenate was prepared and carotid artery blood samples were used for blood gas analysis and oxygenation index (PaO2/FiO2) calculation. The levels of tumour necrosis factor alpha (TNF-α), interleukin (IL) 6 and IL-10 in serum and the levels of cysteine protease 3 (caspase-3), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD) in lung tissues were examined. The wet-dry ratio (W/D) and water content of the lung tissue were calculated, and the TUNEL method was used to determine the rate of lung tissue apoptosis in each group. Tissue specimens were obtained from the partial lung for histopathological examination. Results: Compared with those in group A, the water content of the lung tissue, the rate of lung tissue apoptosis, W/D and the caspase-3, TNF-α, IL-6, IL-10, MDA and MPO levels were significantly greater in other groups (PP< 0.05). Compared with those in group B, the levels of W/D, the water content of the lung tissue, the rate of lung tissue apoptosis and the levels of caspase-3, TNF-α, IL-6, MDA and MPO were significantly low (P and the levels of IL-10, SOD and PaO2/FiO2 were significantly high in groups C and D (P The expression of the aforementioned factors was more evident in Group D (P < 0.05). Histopathological examination revealed that groups C and D had greater levels of inflammatory granulocytes than group B. This was more evident in group D. Conclusions: The inhalation of edaravone can reduce smoke inhalation-induced lung injury. This may be related to the inhibition of apoptosis, the reduction of peroxidation injury and the production/release of inflammatory mediators/free radicals. It exerts a remarkable preventive effect.

Effects of Budesonide Aerosol Inhalation on Perioperative Lung Function in Patients Undergoing Cardiopulmonary Bypass Valve Replacement

[Objectives]To explore the effects of budesonide aerosol inhalation on the perioperative pulmonary function of patients undergoing cardiopulmonary bypass valve replacement.[Methods]A total of 82 patients who underwent cardiopulmonary bypass valve replacement during January 2018 and May 2019 in the Affiliated Hospital of Chengde Medical College were selected.They were divided into blank control group(group A,n=28),aerosol control group(group B,n=27,normal saline aerosol treatment),and experimental group(group C,n=27,budesonide aerosol treatment)by the random number table method.Corresponding treatments were given 5 d before surgery and 5 d after surgery,and the treatment effects of the 3 groups were compared.[Results]The clinical symptom scores of the patients in the experimental group were significantly lower than those in the blank control group and the aerosol control group,and the total effective rate of treatment was significantly higher than that in the blank control group.[Conclusions]Perioperative application of budesonide aerosol inhalation can effectively improve the clinical symptoms,treatment effect,and clinical prognosis of patients undergoing cardiopulmonary bypass valve replacement.

Analysis of the Effect of Anesthetics Comprising of Remifentanil Combined with Propofol During Thyroidectomy

Objective:To analyze the anesthetic effect of remifentanil combined with propofol during thyroidectomy.Methods:A total of 70 patients who underwent thyroidectomy during November 2018 to November 2019 in Chongqing Eleventh People’s Hospital were selected and recruited.These patients were divided into control group and observation group by random number table method.Each group consisted of 35 patients.The patients in the control group was given intravenous anesthesia comprising of propofol combined with intermittent fentanyl anesthesia,whereas the patients in the observation group was given intravenous anesthesia comprising of remifentanil combined with propofol.Results:The heart rate and mean arterial pressure of the observation group after anesthesia for 30 minutes were lower than those of the control group,and the differences were statistically significant(P<0.05).The total incidence of adverse reactions in the observation group was lower than that of the control group,and the differences were statistically significant(P<0.05).Conclusion:Remifentanil combined with propofol is effective in thyroidectomy.This combination can reduce the risk of adverse reactions and maintain stable hemodynamic parameters.

New-Type Inhalation For Bronchial Asthma

Aiqun Brand Bronchial Astnma Inhalation (Kechuan Biwen’an) developed by the Hunan Xiangheng Pharmaceutical Factory is prepared and produced with the elements necessary to the body, and many kinds of traditional Chinese medicinal herbs, according to a scientific prescription. It is used to treat acute and chronic bronchitis, bronchial asthma, pulmonary emphysema, allergic rhinitis, and chronic pharyngitis

A Genetic Susceptibility Study of Lung Cancer Risk Potentially Associated with Polycyclic Aromatic Hydrocarbon Inhalation Exposure

For lifetime non-smokers, lung cancer risk is mainly associated with inhalation exposure to air pollution. For the Chinese population, indoor air pollution due to solid fuel combustion has been the primary source of inhalation exposure for decades. Polycyclic aromatic hydrocarbons （PAHs） are the by-products of incomplete combustion.

Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury

AIM:To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shockinduced lung and intestine injuries.METHODS:Wistar male rats were randomly divided into four groups:control group(Group A,n = 15);septic shock group(Group B,n = 15);early fluid resuscitation-treated septic shock group(Group C,n = 15);and early fluid resuscitation and inhalation of 2% hydrogentreated septic shock group(Group D,n = 15).The activity of hydroxyl radicals,myeloperoxidase(MPO),superoxide dismutase(SOD),diamine oxidase(DAO),and the concentration of malonaldehyde(MDA) in the lung and intestinal tissue were assessed according to the corresponding kits.Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine.The expression levels of interleukin(IL)-6,IL-8,and tumor necrosis factor(TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method.The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting.RESULTS:Septic shock elicited a significant increase in the levels of MDA(10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO(6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues.These effects were not significantly decreased by Group C pretreatment,but were significantly reduced by Group D pretreatment(MDA:4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein;MPO:2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue).The activity of SOD(250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock,and was not significantly increased by Group C pretreatment,but was significantly enhanced by Group D pretreatment(331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein).Histological evidence of lung hemorrhage,neutrophil infiltration and overexpression of IL-6,IL-8,and TNF-α was observed in lung tissues,all of which were attenuated by Group C and further alleviated by Group D pretreatment.Septic shock also elicited a significant increase in the levels of MDA,MPO and DAO(6.54 ± 0.68 kU/L vs 4.32 ± 0.33 kU/L) in intestinal tissues,all of which were further increased by Group C,but significantly reduced by Group D pretreatment.Increased Chiu scoring and overexpression of IL-6,IL-8 and TNF-α were observed in intestinal tissues,all of which were attenuated by Group C and further attenuated by Group D pretreatment.CONCLUSION:Combined early fluid resuscitation and hydrogen inhalation may protect the lung and intestine of the septic shock rats from the damage induced by oxidative stress and the inflammatory reaction.

Histomorphological and Histochemical Alterations Following Short-term Inhalation Exposure to Sulfur Mustard on Visceral Organs of Mice

Toxic effects of inhaled sulfur mustard (SM) on the histology of visceral organs was investigaed by exposing mice to 84. 6mg/m3 for 1h duration, using controlled single exposure conditions. A progressive fall in body weight from third day onwards was noticed. Light microscopic examination of the pulmonary tissue of these animals at 6 h post exposure revealed that the tracheobronchial epithelium remained intact, but was infiltrated by inflammatory cells. By 24 h post exposure, the mucosecretory cells were destroyed. The indanunatory reaction was maximum at 48 h. By 7th day post exposure there was swelling and vacuolation of lung parenchymal cells and thrombi formation. In addition SM caused congestion and hemorrhage at alveolar level. SM also caused granulovacuolar degeneration with perinuclear clumping of the cytopasm of hepatocytes and renal parenchymal cells. Renallesions were chazacterized by congestion and hemorrhage. Among visceral tissues, maximum atrophywas observed in spleen. Distribution of lesions increased with post exposure period. The maximum lesions were observed at 7th day post-exposure.

Practical,regulatory and clinical considerations for development of inhalation drug products

The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction.From the points of formulation,device and patient use,this article summarizes the inhalation drugs,including pressurized metered dose inhaler(pMDI),dry powder inhaler(DPI),and nebulizer that are currently available in the US and UK markets.It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA(U.S.Food and Drug Administration)and the EMA(European Medicines Agency).